Homocysteine Levels (homocysteine + level)

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Homocysteine Levels

  • plasma homocysteine level


  • Selected Abstracts


    Homocysteine Level and Cognitive Function in Patients with Arterial Disease: The Second Manifestations of ARTerial Disease Study

    JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 4 2006
    Fleur van A. Raamt MD
    OBJECTIVES: To assess the relationship between total plasma homocysteine (tHcy) level and cognitive function in patients with manifest arterial disease. DESIGN: Cross-sectional. SETTING: Patients with symptomatic cerebrovascular disease, cardiovascular disease, peripheral arterial disease, or abdominal aortic aneurysm included in the Second Manifestations of ARTerial disease study, a single-center, longitudinal study with an extensive screening program at baseline. PARTICIPANTS: Three hundred forty-five consecutively included patients, mean age 59. MEASUREMENTS: The patients underwent an extensive neuropsychological test. The cognitive domains assessed were memory, executive function, attention, and visuoperception and construction. Each raw score was transformed into standardized z-scores, and a sum score for global cognitive function was determined. Risk factors and vascular damage were measured in detail. RESULTS: Linear regression showed that elevated levels of tHcy were related to lower global cognitive function (,=,0.065, 95% confidence interval (CI)=,0.116 to ,0.013) and, more specifically, lower performance on memory (,=,0.078, 95% CI=,0.155 to ,0.002), attention (,=,0.079, 95% CI=,0.163 to ,0.005), and visuoperception and construction (,=,0.125, 95% CI=,0.236 to ,0.014) per standard deviation increase in tHcy (SD=6.4 mol/L), after adjustment for age, sex, educational level, extent of atherosclerosis, and location of vascular disease. Silent cerebral infarcts did not influence this relationship. CONCLUSION: A relationship was found between tHcy levels and cognitive function that was independent of extent and location of arterial disease. The results suggest that vascular mechanisms are not responsible for the relationship between tHcy and cognitive function. [source]


    Effect of Chronic Alcohol Consumption on Total Plasma Homocysteine Level in Rats

    ALCOHOLISM, Issue 3 2000
    Felix Stickel
    Background: Chronic alcoholism in humans is associated with the development of hyperhomocysteinemia, the mechanism of which remains unclear. Among the causes of hyperhomocysteinemia is depletion of folate, vitamin B12, or vitamin B6, Population-based studies indicate that folate is the strongest vitamin determinant of hyperhomocysteinemia and, in most settings, folate supplementation effectively lowers elevated homocysteine levels. However, it is not clear whether folate deficiency is the cause of alcoholrelated hyperhomocysteinemia. Methods: In the present study, 10 male Sprague Dawley® rats were fed ethanol-containing Lieber- DeCarli diets with 13 mg of folic acid per kilogram of diet. This represents a folate intake more than 20 times the basal requirement. Ethanol represented 36% of total energy, which yielded a concentration of 6.2% (vol/vol). The same number of rats were pair-fed with isocaloric control diets that contained an identical level of folate in which ethanol was entirely replaced by maltodextrin. Results: At the end of 4 weeks, alcohol-fed rats did not show any significant reduction in plasma or hepatic folate concentrations, plasma pyridoxal-5,-phosphate concentration, or plasma vitamin B12 concentration. On the other hand, alcohol-fed rats were significantly hyperhomocysteinemic (17.24 ± 4.63 ,mol/liter,p < 0.01) compared to the nonalcohol group (10.73 ± 2.76 ,mol/liter). Alcohol-fed rats also had a significantly lower hepatic S-adenosylmethionine and higher hepatic S-adenosylhomocysteine levels. Conclusions: Chronic alcohol consumption produces hyperhomocysteinemia by a mechanism that is related to interference with one-carbon metabolism, and not through vitamin depletion. [source]


    Homocysteine levels in patients with risk factors for atherosclerosis

    CLINICAL CARDIOLOGY, Issue 6 2001
    Arnon Blum M.D.
    Abstract Background: Abundant epidemiological evidence has demonstrated that the presence of mild to moderate hyperhomocysteinemia is an independent risk factor for atherosclerosis in the coronary, cerebral, and peripheral vasculature, and for vascular disease, including coronary disease. It has been demonstrated that plasma total homocysteine level is a strong predictor of mortality in patients with angiographically confirmed coronary artery disease. Hypothesis: The study was undertaken to determine the extent of homocysteine levels in patients without documented coronary artery disease, but with at least one risk factor for atherosclerosis. Methods: Fasting blood samples were collected prospectively from 160 consecutive patients (50 women and 110 men, mean age 65 ± 7 years) who had at least one risk factor for atherosclerosis, but had no documented coronary artery disease. Homocysteine levels were measured by an immunoassay method. Results: Of the patients studied, 78 (48.75%) with at least one risk factor for atherosclerosis had high homocysteine levels; 62 patients had mild hyperhomocysteinemia (15,30 ,mol/l); and 16 patients had moderate hyperhomocysteinemia (30,100 ,mol/l). Conclusions: Our data suggest that hyperhomocysteinemia is highly prevalent in patients with risk factors for atherosclerosis. Homocysteine level (an independent convertible risk factor to atherosclerosis) should be measured routinely in patients with risk factors for atherosclerosis and treated appropriately. [source]


    An Assessment of the Potential Value of Elevated Homocysteine in Predicting Alcohol-withdrawal Seizures

    EPILEPSIA, Issue 5 2006
    Stefan Bleich
    Summary:,Purpose: Higher homocysteine levels were found in actively drinking patients with alcohol dependence. Recent studies have shown that high homocysteine levels are associated with alcohol-withdrawal seizures. The aim of the present study was to calculate the best predictive cutoff value of plasma homocysteine levels in actively drinking alcoholics (n = 88) with first-onset alcohol-withdrawal seizures. Methods: The present study included 88 alcohol-dependent patients of whom 18 patients had a first-onset withdrawal seizure. All patients were active drinkers and had an established diagnosis of alcohol dependence, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Sensitivity and specificity were calculated by using every homocysteine plasma level found in the study population as cut-off value. A Bayes theorem was used to calculate positive (PPV) and negative (NPV) predictive values for all cutoff values used. Results: The highest combined sensitivity and specificity was reached at a homocysteine plasma cutoff value of 23.9 ,M. Positive predictive values ranged from 0.23 to 0.745; the maximum was reached at a homocysteine plasma level of 41.7 ,M. Negative predictive values ranged from 0.50 to 0.935, with a maximum at a homocysteine plasma level of 15.8,M. Conclusions: Homocysteine levels above this cutoff value on admission are a useful screening tool to identify actively drinking patients at higher risk of alcohol-withdrawal seizures. This pilot study gives further hints that biologic markers may be helpful to predict patients at risk for first-onset alcohol-withdrawal seizures. [source]


    Homocysteine levels and sustained virological response to pegylated-interferon ,2b plus ribavirin therapy for chronic hepatitis C: a prospective study

    LIVER INTERNATIONAL, Issue 2 2009
    Guglielmo Borgia
    Abstract Background: Chronic hepatitis C affects about 3% of the world's population. Pegylated interferon (IFN) , plus ribavirin is the gold standard treatment. Methylenetetrahydrofolate reductase(MTHFR) is a key enzyme in the metabolism of homocysteine. MTHFR gene polymorphisms and high levels of homocysteine are associated with a high degree of steatosis and fibrosis, conditions associated with a low sustained virological response (SVR) rate. Aims: To evaluate whether MTHFR polymorphisms and homocysteine levels are predictors of the outcome of treatment in 102 prospectively enrolled patients with chronic hepatitis C naive to treatment. Methods: Patients were treated with pegylated interferon ,-2b plus ribavirin. All patients underwent blood tests, assessment of homocysteine, vitamin B12, folate, hepatitis C virus (HCV)-RNA levels, screening for MTHFR gene polymorphisms and liver ultrasound examination. Results: Homocysteine levels were deranged (>16 ,mol/L) in 10.5% of MTHFR wild-type patients vs 40.3% of non-wild-type patients (P=0.015). Homocysteine levels were 14.4 ,mol/L in SVR patients and 15.5 ,mol/L in non-SVR patients (P=0.049). The SVR rate was 40.0% in MTHFR wild-type patients, 52.0% in heterozygote mutants and 39.3% in homozygote mutants (P=0.467). At logistic regression analysis, genotypes 2 and 3 (odds ratio: 12.328, 95% confidence interval: 3.390,44.837, P=0.0001), homocysteine <16 ,mol/L (odds ratio: 3.397, 95% confidence interval: 1.033,11.177, P=0.044) and aspartate aminotransferase (AST) levels <48 U/L (odds ratio: 3.262, 95% confidence interval: 1.125,9.458, P=0.029) were independent predictors of SVR. Conclusions: In patients with chronic hepatitis C, homocysteine levels are associated with the outcome of pegylated-IFN, plus ribavirin treatment, while polymorphisms of MTHFR are not. [source]


    Homocysteine levels after acute levodopa intake in patients with Parkinson's disease,

    MOVEMENT DISORDERS, Issue 9 2009
    Thomas Müller MD
    Abstract Levodopa (L -dopa) administered with a dopadecarboxylase inhibitor (DDI) increases homocysteine plasma levels. This may support the onset of atherosclerosis-related disorders and neuropsychiatric complications in patients with Parkinson's disease (PD). This homocysteine elevation is considered as long-term effect of chronic L -dopa/DDI treatment. Little is known about the acute effects of L -dopa/DDI intake on homocysteine generation. The objective of this trial was to investigate the relations between L -dopa and homocysteine after acute L -dopa/DDI administration in PD patients with different L -dopa metabolism. Thirty PD patients were divided into groups with superior (I) and less (II) L -dopa absorption after standardized intake of 125 mg L -dopa/benserazide with determination of L -dopa, 3- O -methyl-dopa (3-OMD) and homocysteine in plasma at baseline, 30, 60, and 90 minutes. There was a homocysteine increase in Group I (F = 5; P = 0.005) and a moderate decrease in Group II (F = 4.27; P = 0.01). A rise of 3-OMD (F = 10.51; P < 0.0001) appeared in Group I, but not in Group II (F = 0.91; P = 0.44), accordingly L -dopa accumulation was better in Group I than in Group II. Thus, in conclusion, L -dopa metabolism is an important component for homocysteine elevation after one time L -dopa/DDI administration in PD patients. © 2009 Movement Disorder Society [source]


    Homocysteine metabolism in families from southern Italy with neural tube defects: role of genetic and nutritional determinants

    PRENATAL DIAGNOSIS, Issue 1 2006
    Elvira Grandone
    Abstract Objective To evaluate the role of different polymorphic gene variants involved in homocysteine metabolism and plasma levels of homocysteine, folate and vitamin B12 in families from southern Italy with neural tube defects (NTDs). Methods Eighteen fathers, 15 NTD children and 60 women who had conceived NTD foetuses were investigated. A group of 100 adults and 43 apparently healthy children was used as control. At the time of blood draw, none were taking vitamin pills or nutritional supplements. Results Among controls, 79 (55.2%) were heterozygous for C677T MTHFR variant and 26 (18.2%) were TT homozygous. Among the cases, 35 (61.4%) out of 57 mothers and 7 (38.9%) out of 18 fathers carried the T allele; 12 (21.1%) mothers and 2 (11.1%) fathers had the TT genotype. Four (26.7%) out of 15 probands were TT homozygous and 11 (73.3%) were heterozygous (Fisher exact test p = 0.025). No significant difference between groups was observed for the 1298C MTHFR variant and CBS haplotypes. Median homocysteine in NTD children was significantly higher (10.0 µmol/L) than that of controls (median 4.5 µmol/L, Mann,Whitney p < 0.05). Folate and B12 were not different among groups. Conclusions The T677 MTHFR allele is significantly associated with the occurrence of NTDs; no significant association has been observed with other genetic determinants analysed. Homocysteine levels in children with NTDs are significantly higher than those of the paediatric population from the same geographical area. Copyright © 2006 John Wiley & Sons, Ltd. [source]


    Homocysteine levels in patients with risk factors for atherosclerosis

    CLINICAL CARDIOLOGY, Issue 6 2001
    Arnon Blum M.D.
    Abstract Background: Abundant epidemiological evidence has demonstrated that the presence of mild to moderate hyperhomocysteinemia is an independent risk factor for atherosclerosis in the coronary, cerebral, and peripheral vasculature, and for vascular disease, including coronary disease. It has been demonstrated that plasma total homocysteine level is a strong predictor of mortality in patients with angiographically confirmed coronary artery disease. Hypothesis: The study was undertaken to determine the extent of homocysteine levels in patients without documented coronary artery disease, but with at least one risk factor for atherosclerosis. Methods: Fasting blood samples were collected prospectively from 160 consecutive patients (50 women and 110 men, mean age 65 ± 7 years) who had at least one risk factor for atherosclerosis, but had no documented coronary artery disease. Homocysteine levels were measured by an immunoassay method. Results: Of the patients studied, 78 (48.75%) with at least one risk factor for atherosclerosis had high homocysteine levels; 62 patients had mild hyperhomocysteinemia (15,30 ,mol/l); and 16 patients had moderate hyperhomocysteinemia (30,100 ,mol/l). Conclusions: Our data suggest that hyperhomocysteinemia is highly prevalent in patients with risk factors for atherosclerosis. Homocysteine level (an independent convertible risk factor to atherosclerosis) should be measured routinely in patients with risk factors for atherosclerosis and treated appropriately. [source]


    The effects of tobacco smoke on the homocysteine level,a risk factor of atherosclerosis

    ADDICTION BIOLOGY, Issue 2 2003
    ANDRZEJ SOBCZAK
    Homocysteine may promote atherogenesis and thrombogenesis. There is evidence from case,control and cross-sectional cohort studies that there is a positive association between plasma homocysteine levels and coronary artery disease, cerebrovascular disease and peripheral vascular disease. There is also some evidence that certain life-style factors such as cigarette smoking may affect homocysteine levels. In this work is presented a review of recent opinion about the influence of tobacco smoking on homocysteine levels. [source]


    Methylenetetrahydrofolate reductase gene and risk of Alzheimer's disease in Koreans

    INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2008
    Jae-Min Kim
    Abstract Background The association between methylenetetrahydrofolate reductase (MTHFR) c.677C,>,T (A222V) polymorphism and Alzheimer's disease (AD) is controversial. The objectives of the study were to investigate the association between MTHFR c.677C,>,T polymorphism and AD in Korean elders and to the extent to which it is modified by the major components of one-carbon metabolism and apolipoprotein E (APOE) genotype. Methods Seven hundred and thirty-two community residents aged 65 or over were clinically assessed for AD. Genotyping was performed for MTHFR c.677C,>,T and APOE; serum levels of folate, vitamin B12, and homocysteine were assayed. Age, gender and education were included as covariates. Results A trend of association between TT genotype of MTHFR c.677C,>,T and AD was found [adjusted OR (95% CI): 1.73 (0.80,3.74)]. The association was significant in the presence of below-median vitamin B12 level [3.66 (1.14,11.71)] and in APOE e4 non-carriers [2.97 (1.00,8.55)] with significant interaction terms, and bordered on significance in the presence of above-median homocysteine level [2.73 (0.94,7.90)]. Conclusions These findings suggest gene-environment and gene-gene interactions on the risk of AD in Koreans. Copyright © 2007 John Wiley & Sons, Ltd. [source]


    Low Dietary Riboflavin but Not Folate Predicts Increased Fracture Risk in Postmenopausal Women Homozygous for the MTHFR 677 T Allele,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2008
    Nahid Yazdanpanah
    Abstract The MTHFR C677T polymorphism is associated with mildly elevated homocysteine levels when folate and/or riboflavin status is low. Furthermore, a mildly elevated homocysteine level is a risk factor for osteoporotic fractures. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T variant on fracture risk in 5035 men and women from the Rotterdam Study. We found that the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women. Introduction: The MTHFR C677T polymorphism is associated with mildly elevated homocysteine (Hcy) levels in the presence of low folate and/or riboflavin status. A mildly elevated Hcy level was recently identified as a modifiable risk factor for osteoporotic fracture. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T polymorphism on BMD and fracture risk. Materials and Methods: We studied 5035 individuals from the Rotterdam Study, ,55 yr of age, who had data available on MTHFR, nutrient intake, and fracture risk. We performed analysis on Hcy levels in a total of 666 individuals, whereas BMD data were present for 4646 individuals (2692women). Results: In the total population, neither the MTHFR C677T polymorphism nor low riboflavin intake was associated with fracture risk and BMD. However, in the lowest quartile of riboflavin intake, female 677- T homozygotes had a 1.8 (95% CI: 1.1-2.9, p = 0.01) times higher risk for incident osteoporotic fractures and a 2.6 (95% CI: 1.3-5.1, p = 0.01) times higher risk for fragility fractures compared with the 677-CC genotype (interaction, p = 0.0002). This effect was not seen for baseline BMD in both men and women. No significant influence was found for dietary folate intake on the association between the MTHFR C677T genotype and fracture risk or BMD. In the lowest quartile of dietary riboflavin intake, T-homozygous individuals (men and women combined) had higher (22.5%) Hcy levels compared with C-homozygotes (mean difference = 3.44 ,M, p = 0. 01; trend, p = 0.02). Conclusions: In this cohort of elderly whites, the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women. [source]


    C677T polymorphism of methylenetetrahydrofolate reductase gene affects plasma homocysteine level and is a genetic factor of late-onset Alzheimer's disease

    PSYCHOGERIATRICS, Issue 1 2004
    Tomoyuki KIDA
    Abstract Background:, Elevated plasma homocysteine levels are known as a risk for atherosclerotic vascular disease and venous thrombosis and have been shown as a risk for late-onset Alzheimer's disease (LOAD). Method:, To examine the effect of genetic factors predisposing to elevated plasma homocysteine levels on the occurrence of LOAD, we determined the genotype of a C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene and a variable number tandem repeat (VNTR) spanning exon 13,intron 13 boundary of cystathionine ,-synthase (CBS) gene in patients with LOAD and community-based control subjects. Results:, Logistic regression indicated that the MTHFR-T allele was a risk for LOAD (P < 0.05), independently from apolipoprotein E-,4 (APOE-,4) allele. Kaplan,Meier tests showed that in APOE-,4 non-carriers, individuals with the MTHFR-TT genotype have occurences of LOAD earlier than those with the MTHFR-CC genotype (P < 0.05). Multiple regression analysis indicates that MTHFR-T allele increases plasma homocysteine levels (P = 0.0002), while the number of X chromosomes decreases (P = 0.01). Plasma homocysteine level was not correlated with age, plasma albumin reflecting nutritional condition, and the dose of APOE-,4 allele. The CBS-20 VNTR allele showed the same trend to increase plasma homocysteine level as the MTHFR-T allele, but a risk effect for LOAD was not evident. Conclusion:, A genetic propensity for elevated plasma homocysteine levels, explained by the MTHFR-T allele encoding defective enzymatic function, is involved in the development of LOAD, particularly in APOE-,4 non-carriers, and that homocysteine metabolism could be a preventive target to LOAD in the elderly. [source]


    Effects of antiepileptic drugs on lipids, homocysteine, and C-reactive protein,

    ANNALS OF NEUROLOGY, Issue 4 2009
    Scott Mintzer MD
    Objective The widely prescribed anticonvulsants phenytoin and carbamazepine are potent inducers of cytochrome P450 enzymes, which are involved in cholesterol synthesis. We sought to determine whether these drugs have an effect on cholesterol and other serological markers of vascular risk. Methods We recruited 34 epilepsy patients taking carbamazepine or phenytoin in monotherapy whose physicians had elected to change treatment to one of the noninducing anticonvulsants lamotrigine or levetiracetam. Fasting blood samples were obtained both before and 6 weeks after the switch to measure serum lipid fractions, lipoprotein(a), C-reactive protein, and homocysteine. A comparator group of 16 healthy subjects underwent the same serial studies. Results In the epilepsy patients, switch from either phenytoin or carbamazepine produced significant declines in total cholesterol (,24.8mg/dl), atherogenic (non,high-density lipoprotein) cholesterol (,19.9mg/dl), triglycerides (,47.1mg/dl) (all p < 0.0001), and C-reactive protein (,31.4%; p = 0.027). Patients who stopped taking carbamazepine also had a 31.2% decline in lipoprotein(a) level (p = 0.0004), whereas those taken off phenytoin had a decrease in homocysteine level (,1.7,mol/L; p = 0.005). All of these changes were significant when compared with those seen in healthy subjects (p < 0.05). Results were similar whether patients were switched to lamotrigine or levetiracetam. Interpretation Switching epilepsy patients from the enzyme-inducers carbamazepine or phenytoin to the noninducing drugs levetiracetam or lamotrigine produces rapid and clinically significant amelioration in several serological markers of vascular risk. These findings suggest that phenytoin and carbamazepine may substantially increase the risk for cardiovascular and cerebrovascular disease. Ann Neurol 2009;65:448,456 [source]


    Asymmetric Dimethylarginine in Hemodialysis, Hemodiafiltration, and Peritoneal Dialysis

    ARTIFICIAL ORGANS, Issue 5 2010
    Jaromķr Eiselt
    Abstract Asymmetric dimethylarginine (ADMA) is a mediator of endothelial dysfunction. Production and elimination of ADMA may be affected by the type of renal replacement therapy used and oxidative stress. Plasma ADMA, advanced glycation end products (AGE), and homocysteine were assessed in 59 subjects: 20 hemodialysis (HD) patients, 19 patients undergoing peritoneal dialysis (PD), and 20 controls. Results were compared between the groups. The effect of 8 weeks of HD and high-volume predilution hemodiafiltration (HDF) was compared in a randomized study. HD patients showed higher ADMA (1.20 [0.90,1.39 µmol/L]) compared to controls (0.89 [0.77,0.98], P < 0.01), while ADMA in PD did not differ from controls (0.96 [0.88,1.28]). AGE and homocysteine were highest in HD, lower in PD (P < 0.01 vs. HD), and lowest in controls (P < 0.001 vs. HD and PD). PD patients had higher residual renal function than HD (P < 0.01). The decrease in ADMA at the end of HD (from 1.25 [0.97,1.33] to 0.66 [0.57,0.73], P < 0.001) was comparable to that of HDF. Switching from HD to HDF led to a decrease in predialysis homocysteine level in 8 weeks (P < 0.05), while ADMA and AGE did not change. Increased ADMA levels in patients undergoing HD, as compared to PD, may be caused by higher oxidative stress and lower residual renal function in HD. Other factors, such as diabetes and statin therapy, may also be at play. The decrease in ADMA at the end of HD and HDF is comparable. Switching from HD to HDF decreases in 8 weeks the predialysis levels of homocysteine without affecting ADMA. [source]


    Homocysteine levels in patients with risk factors for atherosclerosis

    CLINICAL CARDIOLOGY, Issue 6 2001
    Arnon Blum M.D.
    Abstract Background: Abundant epidemiological evidence has demonstrated that the presence of mild to moderate hyperhomocysteinemia is an independent risk factor for atherosclerosis in the coronary, cerebral, and peripheral vasculature, and for vascular disease, including coronary disease. It has been demonstrated that plasma total homocysteine level is a strong predictor of mortality in patients with angiographically confirmed coronary artery disease. Hypothesis: The study was undertaken to determine the extent of homocysteine levels in patients without documented coronary artery disease, but with at least one risk factor for atherosclerosis. Methods: Fasting blood samples were collected prospectively from 160 consecutive patients (50 women and 110 men, mean age 65 ± 7 years) who had at least one risk factor for atherosclerosis, but had no documented coronary artery disease. Homocysteine levels were measured by an immunoassay method. Results: Of the patients studied, 78 (48.75%) with at least one risk factor for atherosclerosis had high homocysteine levels; 62 patients had mild hyperhomocysteinemia (15,30 ,mol/l); and 16 patients had moderate hyperhomocysteinemia (30,100 ,mol/l). Conclusions: Our data suggest that hyperhomocysteinemia is highly prevalent in patients with risk factors for atherosclerosis. Homocysteine level (an independent convertible risk factor to atherosclerosis) should be measured routinely in patients with risk factors for atherosclerosis and treated appropriately. [source]


    Homozygous thermolabile variant of the methylenetetrahy-drofolate reductase gene: a potential risk factor for hyperhomo-cysteinaemia, CVD, and stroke in childhood

    DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2001
    Mara Prengler
    In this study of 118 children (median age 5.1 years; range 6 months to 17 years) with ischaemic stroke or transient ischaemic attack (TIA), 22 children (19%) were homozygous for the thermolabile variant of the methylenetetrahydrofolate reductase allele (t-MTHFR), compared with nine of 78 (12%) of a reference population (p=0.18, OR 1.76, 95% CI 0.76 to 4.04). Of those with cerebrovascular disease (CVD), 17 of 84 were homozygous for the t-MTHFR allele (p=0.13 compared with the reference population (OR 1.95, 95% CI 0.81 to 4.65). There was a significant (p<0.025) increment of plasma total homocysteine concentration in homozygotes for the t-MTHFR allele compared with heterozygotes, negatives for the t-MTHFR allele, and control children with no history of stroke. In four of 12 homozygotes for the t-MTHFR allele, plasma homocysteine levels were raised, compared with three of 38 of those who were negative or heterozygous (p=0.047; OR 5.8, 95% CI 1.1 to 31.2). Homozygotes for the t-MTHFR allele were significantly more likely to have a recurrent event than those who were negative or heterozygous (Cox regression p=0.031, hazard ratio 2.18, 95% CI 1.08 to 4.42). These data suggest that homozygosity for the t-MTHFR allele is associated with raised homocysteine levels in children and is a risk factor for primary and secondary stroke and TIA. [source]


    Reduced plasma total homocysteine concentrations in Type 1 diabetes mellitus is determined by increased renal clearance

    DIABETIC MEDICINE, Issue 3 2005
    B. A. J. Veldman
    Abstract Introduction Elevated plasma levels of total homocysteine are related to the development of vascular complications. Patients with diabetes mellitus are particularly at risk for the development of these complications. Several factors determine plasma total homocysteine including renal function. Aims As early Type 1 diabetes is characterized by a relative glomerular hyperfiltration, increased renal clearance could contribute to decreased levels of homocysteine as observed in Type 1 diabetes mellitus. Therefore we investigated the relationship between plasma total homocysteine and the glomerular filtration rate (GFR). Methods In 92 Type 1 diabetes patients and 44 control subjects, we measured GFR and effective renal plasma flow (ERPF) by means of continuous infusion of inulin and p-aminohippurate. Fasting plasma total homocysteine was measured using high performance liquid chromatography. Results GFR (121 ± 21 resp. 104 ± 14 ml/min; P < 0.001) and ERPF (563 ± 127 resp. 516 ± 121 ml/min; P = 0.05) were significantly higher in Type 1 diabetes patients as compared with control subjects. Plasma total homocysteine was reduced in Type 1 diabetes patients as compared with control subjects (11.0 ± 4.5 resp. 13.4 ± 7 µmol/l; P = 0.01). Plasma total homocysteine was strongly correlated with GFR (Type 1 diabetes patients: r = ,0.43, P < 0.001; control subjects: r = ,0.39, P = 0.01). Conclusion GFR is a major determinant of plasma total homocysteine levels in Type 1 diabetes patients as well as control subjects. The reduced plasma total homocysteine levels in diabetes patients can be explained by an increased GFR. [source]


    An Assessment of the Potential Value of Elevated Homocysteine in Predicting Alcohol-withdrawal Seizures

    EPILEPSIA, Issue 5 2006
    Stefan Bleich
    Summary:,Purpose: Higher homocysteine levels were found in actively drinking patients with alcohol dependence. Recent studies have shown that high homocysteine levels are associated with alcohol-withdrawal seizures. The aim of the present study was to calculate the best predictive cutoff value of plasma homocysteine levels in actively drinking alcoholics (n = 88) with first-onset alcohol-withdrawal seizures. Methods: The present study included 88 alcohol-dependent patients of whom 18 patients had a first-onset withdrawal seizure. All patients were active drinkers and had an established diagnosis of alcohol dependence, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Sensitivity and specificity were calculated by using every homocysteine plasma level found in the study population as cut-off value. A Bayes theorem was used to calculate positive (PPV) and negative (NPV) predictive values for all cutoff values used. Results: The highest combined sensitivity and specificity was reached at a homocysteine plasma cutoff value of 23.9 ,M. Positive predictive values ranged from 0.23 to 0.745; the maximum was reached at a homocysteine plasma level of 41.7 ,M. Negative predictive values ranged from 0.50 to 0.935, with a maximum at a homocysteine plasma level of 15.8,M. Conclusions: Homocysteine levels above this cutoff value on admission are a useful screening tool to identify actively drinking patients at higher risk of alcohol-withdrawal seizures. This pilot study gives further hints that biologic markers may be helpful to predict patients at risk for first-onset alcohol-withdrawal seizures. [source]


    Relevance of post-methionine homocysteine and lipoprotein (a) in evaluating the cardiovascular risk in young CAD patients

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2005
    R. Marcucci
    Abstract Background, Aims of our study were to evaluate the prevalence of high lipoprotein (a) [Lp(a)] and homocysteine levels , both in the fasting state (FHcy) and post-methionine (PMHcy) , in young coronary artery disease (CAD) patients, and to investigate the role of genetic and environmental factors for hyperhomocysteinaemia. Materials and methods, We studied 140 patients with angiographically documented CAD (24 women , 55 years and 116 men , 50 years) and 140 healthy subjects as controls. Results, Both FHcy [13·2 (5·4,45·8) vs. 9·0 (5·1,24) µmol L,1); P < 0·0001] and PMHcy [(39·4 (9·0,66·4) vs. 25·2 (16·4,33·9); P < 0·0001] were significantly higher in patients than in controls. Lp(a) levels were significantly higher in patients than in controls (200 (3,1486) mg L,1 vs. 97 (10,412) mg L,1; P < 0·0001). At the multivariate analysis, adjusted for the classical cardiovascular risk factors and creatinine levels, the OR (95% CI) for CAD at young age significantly increased in the fourth quartile of the distribution of FHcy, PMHcy and Lp(a) levels [FHcy: 14·9 (4·1,58), P < 0·0001; PMHcy: 19·2 (4·0,86·3); P < 0·0001; Lp(a): 19·6 (4·7,78·6): < 0·0001]. Vitamin deficiencies were detected in 28/140 (20%) patients. The prevalence of the homozygous C677T (+/+) methylenetetrahydrofolatereductase genotype was higher, but not significantly different, in patients (22·8%) than in controls (18·6%). The allele frequency of the 844ins68 insertion variant in the cystathionine beta-synthase gene was 0·08 in the control group and 0·06 in the patient group. Conclusions, Results of the present study indicate the usefulness of including fasting and post-methionine Hcy, and Lp(a) determination in the diagnostic panels of young CAD patients, in order to obtain a better assessment of their cardiovascular risk profile. [source]


    Methylenetetrahydrofolate reductase gene C677T mutation is related to the defects in the internal elastic lamina of the artery wall

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2002
    P. Hämelahti
    Abstract Background The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene leads to C/C, C/T and T/T genotypes, which affect the plasma homocysteine concentration in humans. In mini-pigs, high serum homocysteine levels are associated with defects in the internal elastic lamina (IEL) of the artery wall, which are apparently related to the migration of smooth muscle cells into the intima during atherogenesis. We studied the association between the MTHFR genotypes and the number of gaps in the IEL in the wall of the five major abdominal arteries. Materials and methods The autopsy study included 123 subjects (90 males and 33 females) aged 18,93. For the light microscopy, a 0·5 cm circular segment of the coeliac, the superior mesenteric, the inferior mesenteric and the renal arteries were cut and embedded in paraffin blocks. The circumference of the IEL, the thickness of the intima and the number of the gaps per millimetre in the IEL were measured by MOP 3 image analysis. Results The T-allele carriers (C/T and T/T) of the MTHFR gene had significantly less gaps in the IEL than the subjects with the C/C genotype in the superior mesenteric and in the left renal arteries (2·02 ± 2·25 vs. 2·53 ± 1·89, P < 0·04 and 0·56 ± 1·09 vs. 1·82 ± 2·66, P < 0·02, respectively). The trend was similar for the coeliac and the right renal arteries. Conclusions Our result suggests that MTHFR polymorphism may be involved in the fragmentation of the IEL. [source]


    The effects of tobacco smoke on the homocysteine level,a risk factor of atherosclerosis

    ADDICTION BIOLOGY, Issue 2 2003
    ANDRZEJ SOBCZAK
    Homocysteine may promote atherogenesis and thrombogenesis. There is evidence from case,control and cross-sectional cohort studies that there is a positive association between plasma homocysteine levels and coronary artery disease, cerebrovascular disease and peripheral vascular disease. There is also some evidence that certain life-style factors such as cigarette smoking may affect homocysteine levels. In this work is presented a review of recent opinion about the influence of tobacco smoking on homocysteine levels. [source]


    Plasma total homocysteine levels are associated with advanced leukoaraiosis but not with asymptomatic microbleeds on T2*-weighted MRI in patients with stroke

    EUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2006
    H. Naka
    Both leukoaraiosis and asymptomatic microbleeds are associated with small-artery diseases. Although an association between hyperhomocysteinemia and leukoaraiosis has been reported, no studies have evaluated the association between total homocysteine (tHcy) level and presence of microbleeds in stroke patients. We evaluated the association between tHcy level and leukoaraiosis or microbleeds in stroke patients. In 102 patients with stroke (69.5 ± 10.3 years old, 54 men and 48 women), microbleeds on T2*-weighted MR images were counted, leukoaraiosis on T2-weighted images was graded and fasting plasma tHcy concentrations were measured. Plasma tHcy level was significantly higher in patients with advanced leukoaraiosis than in those without advanced leukoaraiosis (13.9 ± 4.6 ,mol/l vs. 10.2 ± 3.4 ,mol/l, P < 0.0001). Plasma tHcy level was not significantly different in patients with microbleeds and those without microbleeds (11.3 ± 4.1 ,mol/l vs. 11.4 ± 4.3 ,mol/l, P = 0.9441). Elevated tHcy level is significantly and independently associated with advanced leukoaraiosis [odds ratio (OR), 1.330; 95% CI, 1.130,1.565] but not with the presence of microbleeds. Elevated tHcy level appears to be associated with ischemic small-artery disease rather than with bleeding-prone small-artery disease. [source]


    Uremic hyperhomocysteinemia: A randomized trial of folate treatment for the prevention of cardiovascular events

    HEMODIALYSIS INTERNATIONAL, Issue 2 2007
    Areuza C. A. VIANNA
    Abstract Homocysteine is a risk factor for atherosclerosis in the general population, and serum homocysteine levels are almost universally elevated in chronic renal failure patients. When such patients are treated with dialysis, cardiovascular disease accounts for more than 50% of their mortality, which, in some proportion, may be pathophysiologically related to the elevated serum homocysteine levels. From April 2003 to March 2005, we conducted a 2-year, double-blind, randomized, placebo-controlled trial of 186 patients with end-stage kidney disease due to any cause, who were older than 18 years and stable on hemodialysis. Patients were assigned to receive either oral folic acid 10 mg 3 times a week immediately after every dialysis session under nurse supervision or an identical-appearing placebo for the entire study. On admission, plasma total homocysteine (tHcy) levels were above 13.9 ,mol/L in 96.7% of patients (median 25.0 ,mol/L, range 9.3,104.0 ,mol/L). In the placebo group, tHcy levels remained elevated at 6, 12, and 24 months, while oral folate significantly decreased tHcy to a median value of 10.5 (2.8,20.3) ,mol/L, (p<0.01). During the study, 38 patients (folic acid group 17 vs. placebo group 21; p=0.47) died from cardiovascular disease. Kaplan,Meier life table analysis dealing with the incidence of cardiovascular events, both fatal and nonfatal (myocardial infarction, arrhythmias, angina, heart failure, cerebrovascular accident), showed that 2 years of folic acid treatment and the lowering of the homocysteine blood levels had no effect on cardiovascular events (p=0.41; hazard ratio 1.24, 95% CI 0.74,2.10). However, the carotid artery intima-media wall thickness measured in a blinded fashion decreased from 1.94 ± 0.59 mm to 1.67 ± 0.38 mm (p<0.01) after 2 years of folate therapy. In this short-term study of uremic patients, 2 years of folic acid supplementation normalized the tHcy blood levels in 92.3% of patients but did not change the incidence of cardiovascular events compared with the control group. However, ultrasonography of the common carotid arteries performed at entry and 24 months later showed a significant decrease in intima-media thickness with folate supplementation. This suggests that early folate supplementation may benefit patients with chronic renal failure by preventing cardiovascular deterioration. [source]


    Inhibition of adiponectin production by homocysteine: A potential mechanism for alcoholic liver disease,

    HEPATOLOGY, Issue 3 2008
    Zhenyuan Song
    Although recent evidence suggests that down-regulation of production of the adipocyte hormone adiponectin has pathophysiological consequences for the development of alcoholic liver disease (ALD), the underlying mechanisms are elusive. Abnormal hepatic methionine-homocysteine metabolism induced by prolonged alcohol exposure has been reported both in clinical and experimental studies of ALD. Here, we conducted both in vivo and in vitro experiments to examine the effects of prolonged alcohol exposure on homocysteine levels in adipose tissue, its potential involvement in regulating adiponectin production, and the consequences for ALD. Chronic alcohol exposure decreased the circulating adiponectin concentration and adiponectin messenger RNA (mRNA) and protein levels in epididymal fat pads. Alcohol feeding induced modest hyperhomocysteinemia and increased homocysteine levels in the epididymal fat pad, which was associated with decreased mRNA levels of cystationine ,-synthase. Betaine supplementation (1.5%, wt/vol) in the alcohol-fed mice reduced homocysteine accumulation in adipose tissue and improved adiponectin levels. Moreover, exogenous homocysteine administration reduced gene expression, protein levels, and secretion of adiponectin in primary adipocytes. Furthermore, rats fed a high-methionine diet (2%, wt/wt) were hyperhomocysteinemic and had decreased adiponectin levels in both plasma and adipose tissue, which was associated with suppressed AMP-activated protein kinase activation in the liver. Mechanistic studies revealed that both inactivation of the extracellular signal regulated kinase 1/2 pathway and induction of endoplasmic reticulum stress response, specifically C/EBP homologous protein expression, may contribute to the inhibitory effect exerted by homocysteine. Conclusion: Chronic alcohol feeding caused abnormal accumulation of homocysteine in adipocytes, which contributes to decreased adiponectin production in ALD. (HEPATOLOGY 2008.) [source]


    Mechanisms of protection by the betaine-homocysteine methyltransferase/betaine system in HepG2 cells and primary mouse hepatocytes,

    HEPATOLOGY, Issue 5 2007
    Cheng Ji
    Betaine-homocysteine methyltransferase (BHMT) regulates homocysteine levels in the liver. We previously reported that the alteration of BHMT is associated with alcoholic liver steatosis and injury. In this study, we tested whether BHMT protects hepatocytes from homocysteine-induced injury and lipid accumulation. Both BHMT transfectants of HepG2 cells and primary mouse hepatocytes with suppressed BHMT were generated. Comparisons were made between the cell models with respect to their response to homocysteine treatments. Homocysteine metabolism was impaired in HepG2 cells, and the expression of BHMT in HepG2 cells ameliorated the impairment and stabilized the levels of intracellular homocysteine after the addition of exogenous homocysteine. BHMT expression inhibited homocysteine-induced glucose-regulated protein 78 (GRP78) and C/EBP-homologous protein (CHOP) and homocysteine-induced cell death. A betaine treatment protected primary mouse hepatocytes from a homocysteine-induced increase in GRP78 and cell death but not a tunicamycin-induced increase. Homocysteine induced greater CHOP expression (2.7-fold) in BHMT small interfering RNA (siRNA),transfected cells than in a control (1.9-fold). Homocysteine-induced cell death was increased by 40% in the siRNA-treated cells in comparison with the control. Apolipoprotein B (apoB) expression was higher and triglycerides and cholesterol were lower in HepG2 expressing BHMT. In primary mouse hepatocytes, homocysteine induced the accumulation of triglycerides and cholesterol, which was reduced in the presence of betaine. Betaine partially reduced homocysteine-induced sterol regulatory element binding protein 1 expression in HepG2 cells and increased S-adenosylmethionine in primary mouse hepatocytes. Conclusion: The BHMT/betaine system directly protects hepatocytes from homocysteine-induced injury but not tunicamycin-induced injury, including an endoplasmic reticulum stress response, lipid accumulation, and cell death. This system also exhibits a more generalized effect on liver lipids by inducing ApoB expression and increasing S-adenosylmethionine/S-adenosylhomocysteine. (HEPATOLOGY 2007.) [source]


    Effects of a multi-vitamin/mineral supplement on cognitive function and fatigue during extended multi-tasking,

    HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2010
    Crystal F. Haskell
    Abstract Objectives A significant minority of the population consume multi-vitamins/minerals for their putative health benefits, including potentially beneficial effects on cognitive performance, fatigue and mood. The current study investigated the effect of supplementation with a multi-vitamin/mineral on fatigue and cognitive function in healthy females. Methods In this placebo-controlled, double blind, randomized, parallel groups trial the effect of a multi-vitamin/mineral (Supradyn®) was assessed in 216 females aged 25,50 years. Participants attended the laboratory before and 9 weeks after commencing treatment. During both visits cognitive function and the modulation of task related mood/fatigue were assessed in two discrete 20-min assessment periods during which participants completed a four-module version of the Multi-Tasking Framework. Results Those in the vitamin/mineral group exhibited an attenuation of the negative effects of extended task completion on mood/fatigue. Multi-tasking performance for this group was also improved in terms of accuracy across all tasks, and on two of the individual tasks (Mathematical Processing and Stroop) in terms of both faster and more accurate responses. Analysis of a subsection (N,=,102) demonstrated significant reductions in homocysteine levels following the vitamins/mineral supplement. Conclusions These findings suggest that healthy members of the general population may benefit from augmented levels of vitamins/minerals via direct dietary supplementation. Copyright © 2010 John Wiley & Sons, Ltd. [source]


    Normal homocysteine levels in a population of children with inflammatory bowel disease

    INFLAMMATORY BOWEL DISEASES, Issue 6 2005
    Anna Zholudev MPH
    No abstract is available for this article. [source]


    Segmental testicular ischaemia: presentation, management and follow-up

    INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2009
    D. Gianfrilli
    Summary Segmental infarction of the testis is a rare event. Less than 40 cases have been reported in the literature and its aetiology remains largely unknown. The diagnosis is challenging and its identification crucial as partial ischaemia is frequently confused with testicular tumours and unnecessarily treated with orchiectomy. The objectives of this study are to: (i) raise awareness of this rare condition, (ii) provide the distinctive clinical and radiological features enabling pre-operative diagnosis, (iii) promote appropriate screening of causative factors and (iv) propose an alternative management approach to avoid surgery and preserve fertility. We describe three cases of partial testicular ischaemia in men presenting with reduced sperm quality. The cases demonstrate the ultrasound and magnetic resonance imaging appearance of testicular ischaemia. The surveillance strategy adopted for these lesions indicates that over 2 years of follow-up, marginal changes in the lesions can occur. Histology revealed that infiltration by stromal cells, leucocytes and macrophages is responsible for the remodelling of these lesions. Screening of risk factors for thromboembolism revealed that all patients carried a methylenetetrahydrofolate reductase 677C,T (MTHFR) mutation in a gene involved in folate metabolism, and either borderline or elevated homocysteine levels. Distinctive features permit the pre-operative diagnosis of segmental testicular ischaemia. There are sufficient data to assert that a surveillance strategy is safe and feasible. We speculate that the defects in folate metabolism may pre-dispose individuals to the development of testicular infarction and infertility. [source]


    Anticardiolipin antibody and Taiwanese chronic haemodialysis patients with recurrent vascular access thrombosis

    INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 7 2005
    F-R Chuang
    Summary Vascular access failure is a major cause of morbidity in chronic haemodialysis (HD) patients. However, some factors (such as homocysteine levels) are known regarding the risk factors predisposing certain HD patients to vascular access thrombosis (VAT). Immunoglobulin-G anticardiolipin antibody (IgG-ACA) is strongly associated with venous and arterial thrombosis in patients with normal renal function. Previous investigations have reported the characteristics of patients with raised IgG-ACA titre and recurrent VAT of HD in Western countries, but few equivalent studies exist for Taiwan. This retrospective study attempts to determine whether raised IgG-ACA titres are associated with an increased risk of recurrent VAT in chronic HD patients. This study enrolled 483 patients undergoing HD. IgG-ACA titre and hepatitis B&C marker were measured for all patients. A history of recurrent (VAT more than one) and/or VAT was elicited by using information from the patient questionnaires and was verified by means of careful inpatient and outpatient chart review. Raised IgG-ACA titres were present in 21.7% (105/483) of patients. In both groups (raised IgG-ACA and normal IgG-ACA), the type of shunt differed significantly (p = 0.029). In predicting for more or one episodes of VAT by using multiple logistic regression with all significant factors, synthetic graft was also a significant factor (p < 0.0001). The 105 raised IgG-ACA titres and 378 normal IgG-ACA titres were associated between chronic HD patients and recurrent VAT (p = 0.034). In predicting for more or one episode of VAT by using multiple logistic regression with all significant factors, raised IgG-ACA titre was a non-significant factor (p = 0.336). The presence of hepatitis C had a higher percentage in group with raised IgG-ACA titres of HD patients (p = 0.042). In predicting for more or one episode of VAT by using multiple logistic regression with all significant factors, the presence of hepatitis C was also a significant factor (p = 0.022). In conclusion, the prevalence of raised IgG-ACA titres was 21.7% among HD patients. There was a weak association between raised IgG-ACA titre and recurrent VAT and this finding may be the consequence of pathogenetic role of raised IgG-ACA titres in the development of VAT status for chronic HD patients. The presence of hepatitis C was a cofactor. [source]


    Low Dietary Riboflavin but Not Folate Predicts Increased Fracture Risk in Postmenopausal Women Homozygous for the MTHFR 677 T Allele,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2008
    Nahid Yazdanpanah
    Abstract The MTHFR C677T polymorphism is associated with mildly elevated homocysteine levels when folate and/or riboflavin status is low. Furthermore, a mildly elevated homocysteine level is a risk factor for osteoporotic fractures. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T variant on fracture risk in 5035 men and women from the Rotterdam Study. We found that the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women. Introduction: The MTHFR C677T polymorphism is associated with mildly elevated homocysteine (Hcy) levels in the presence of low folate and/or riboflavin status. A mildly elevated Hcy level was recently identified as a modifiable risk factor for osteoporotic fracture. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T polymorphism on BMD and fracture risk. Materials and Methods: We studied 5035 individuals from the Rotterdam Study, ,55 yr of age, who had data available on MTHFR, nutrient intake, and fracture risk. We performed analysis on Hcy levels in a total of 666 individuals, whereas BMD data were present for 4646 individuals (2692women). Results: In the total population, neither the MTHFR C677T polymorphism nor low riboflavin intake was associated with fracture risk and BMD. However, in the lowest quartile of riboflavin intake, female 677- T homozygotes had a 1.8 (95% CI: 1.1-2.9, p = 0.01) times higher risk for incident osteoporotic fractures and a 2.6 (95% CI: 1.3-5.1, p = 0.01) times higher risk for fragility fractures compared with the 677-CC genotype (interaction, p = 0.0002). This effect was not seen for baseline BMD in both men and women. No significant influence was found for dietary folate intake on the association between the MTHFR C677T genotype and fracture risk or BMD. In the lowest quartile of dietary riboflavin intake, T-homozygous individuals (men and women combined) had higher (22.5%) Hcy levels compared with C-homozygotes (mean difference = 3.44 ,M, p = 0. 01; trend, p = 0.02). Conclusions: In this cohort of elderly whites, the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women. [source]