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C Genotype (c + genotype)

Distribution by Scientific Domains

Medical Sciences	93%
Life Sciences	6%

Distribution within Medical Sciences

Gastroenterology & Hepatology	29%
Oncology & Radiotherapy	18%
General & Internal Medicine	6%
8 Other Subdomains	47%

Kinds of C Genotype

chronic hepatitis c genotype

hepatitis c genotype

Selected Abstracts

Association of autoimmune disease-related gene polymorphisms with chronic graft-versus-host disease

BRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2007
Masako Shimada
Summary Chronic graft-versus-host disease (GVHD) is the most common cause of poor outcomes after haematopoietic stem cell transplantation (HSCT), while the pathophysiology of chronic GVHD remains poorly understood. As both chronic GVHD and autoimmune disease share clinical features, we speculated that autoimmune disease-related genes might be candidate chronic GVHD-related genes. Recent large-scale cohort studies showed that Fc receptor-like 3 gene (FCRL3) single nucleotide polymorphism (SNP) and peptidylarginine deiminases citrullinating enzymes 4 gene (PADI4) haplotype were associated with autoimmune disease. The present study investigated the association between polymorphisms of these two genes and the incidence of chronic GVHD. We analysed 123 cases of Japanese human leucocyte antigen-matched sibling recipients and their donors who underwent HSCT. Although PADI4, which is the rheumatoid arthritis-specific related gene, was not associated with the occurrence of chronic GVHD, the recipient FCRL3 -169C/C genotype was significantly less frequent in chronic GVHD patients than in those without chronic GVHD (P = 0·0086). There was no relationship between FCRL3 polymorphism and acute GVHD. As FCRL3 is expressed by B cells and might have an important role in immunoregulation, this significant protective genetic effect raises the question of whether FCRL3 might also be involved in the pathogenesis of chronic GVHD. [source]

The common G-allele of interleukin-18 single-nucleotide polymorphism is a genetic risk factor for atopic asthma.

CLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2006
The SAPALDIA Cohort Study
Summary Background IL-18 is a pleiotrophic cytokine involved in both, T-helper type 1 (Th1) and Th2 differentiation. Recently genetic variants in the IL-18 gene have been associated with increased risk of atopy and asthma. Objective To examine the relationship of a genetic, haplotype-tagging promotor variant ,137G/C in the IL-18 gene with atopic asthma in a large, well-characterized and population-based study of adults. Methods Prospective cohort study design was used to collect interview and biological measurement data at two examination time-points 11 years apart. Multivariate logistic regression analysis was used to assess the association of genotype with asthma and atopy. Results The G-allele of the IL-18 promotor variant (,137G/C) was associated with a markedly increased risk for the prevalence of physician-diagnosed asthma with concomitant skin reactivity to common allergens. Stratification of the asthma cases by skin reactivity to common allergens revealed an exclusive association of IL-18 ,137 G-allele with an increased prevalence of atopic asthma (adjusted odds ratio (OR): 3.63; 95% confidence interval: (1.64,8.02) for GC or GG carriers vs. CC carriers), and no according association with asthma and concomitant negative skin reactivity (adjusted OR: 1.13; 0.66,1.94). The interaction between IL-18 ,137G/C genotype and positive skin prick test was statistically significant (P=0.029). None of 74 incident asthma cases with atopy at baseline exhibited the CC genotype. Conclusion Our results strongly suggest that this variant of the IL-18 gene is an important genetic determinant involved in the development of atopic asthma. [source]

ORIGINAL ARTICLE: Contribution of Interferon-, Receptor 1 Gene Polymorphisms to Pre-Eclampsia in China

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010
Li-Juan Chen
Citation Chen L-J, Gao H, Zhou H, Zou L, Zou P. Contribution of interferon-, receptor 1 gene polymorphisms to pre-eclampsia in China. Am J Reprod Immunol 2010; 63: 331,338 Problem, As gene polymorphisms of cytokines receptors have been found to significantly influence cell responses to cytokines, the aim of this study was to test the hypothesis that IFN-, receptor 1 (IFNGR1) gene polymorphisms may contribute to the pathogenesis of pre-eclampsia. Method of study, One hundred and sixty-four pre-eclamptic patients (121 patients with mild pre-eclampsia and 43 patients with severe pre-eclampsia) and 171 controls were included. Polymorphisms of the IFNGR1 gene at positions ,611, ,270, +56 and +95 were genotyped with the matrix-assisted laser desorption/ionization time of flight mass spectrometry. Results, This study showed a positive association between ,56C/C genotype (OR = 1.7; 95% CI = 1.1,2.7) and pre-eclampsia. Although the genotype frequencies (except for ,56C/C) of the two polymorphisms were comparable between cases and controls, higher frequency of the ,611A/,56C haplotype (OR = 1.450; 95% CI = 1.070,1.966) was noticed in patients versus controls. All patients and controls were homozygous for the ,270T/T and +95T/T genotypes. Specifically, the frequency of the ,56C allele (OR = 1.838; 95% CI = 1.127,2.995) was higher among patients with severe pre-eclampsia. Conclusion, The IFNGR1 gene polymorphisms may contribute to the pathogenesis of pre-eclampsia in our population. [source]

Interleukin-1, and -10 polymorphisms influence erosive reflux esophagitis and gastritis in Taiwanese patients

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2010
Hsin-Hung Cheng
Abstract Background and Aims:,Helicobacter pylori (H. pylori) infection induces cytokine production and is associated with gastrointestinal diseases. This study examined the relationship of gene polymorphisms, including interleukin (IL) -1,, -10, -8, and tumor necrosis factor-, (TNF-,), H. pylori infection, and susceptibility to gastrointestinal disorders in Taiwanese patients. Methods:,IL-1,,511/,31/+3953, -10,1082/,819/,592, -8,251, and TNF-,,308 polymorphisms were assessed in 628 gastrointestinal disease patients, and 176 healthy controls were analyzed using the polymerase chain reaction,restriction fragment length polymorphism method. Results:,IL-1,,511 T/T and ,31 C/C genotypes, and IL-1,,511 T and ,31 C alleles were associated with an increased risk of reflux esophagitis (P = 0.034, odds ratio [OR] = 1.384, 95% confidence interval [CI]: 1.023,1.871; P = 0.031, OR = 1.388, 95% CI: 1.028,1.873; P = 0.044, OR = 1.342, 95% CI: 1.008,1.786; and P = 0.040, OR = 1.349, 95% CI: 1.014,1.796, respectively). No relationship was found between H. pylori infection and the risk of reflux esophagitis. IL-10,819 C/T and -10,592 A/C genotypes and IL-10,1082/,819/,592 ATA/ACC and ATA/GCC haplotypes were associated with an increased risk of gastritis (P = 0.021, OR = 1.721, 95% CI: 1.084,2.733; P = 0.016, OR = 1.766, 95% CI: 1.112,2.805; P = 0.039, OR = 1.662, 95% CI: 1.024,2.697; and P = 0.035, OR = 1.600, 95% CI: 1.024,2.499, respectively). Conclusion:, Among Taiwanese patients, IL-1, and -10 polymorphisms were associated with an increased risk of erosive reflux esophagitis and gastritis, respectively. [source]

Is long-term interferon monotherapy welcome news for older patients with chronic hepatitis C genotype 1?

HEPATOLOGY RESEARCH, Issue 7 2007
Soo R. Kim
No abstract is available for this article. [source]

Efficacy of low dose long-term interferon monotherapy in aged patients with chronic hepatitis C genotype 1 and its relation to alpha-fetoprotein: A pilot study

HEPATOLOGY RESEARCH, Issue 7 2007
Hideyuki Nomura
Aim:, The objective of this study was to examine the efficacy and safety of low dose long-term interferon (IFN) therapy in aged patients with chronic hepatitis C genotype 1. Methods:, The IFN therapy was performed in Shin-Kokura Hospital on 44 patients aged 60 or older with chronic hepatitis C. All patients had high viral loads of genotype 1. Three million units of natural IFN-, was administered intramuscularly or intrasubcutaneously, three times a week for three years. A control group of 44 subjects not treated with IFN, matched for age, gender and hepatic histology, was formed. Results:, Two of the 44 patients showed a sustained virological response. Alanine aminotransferase was below the upper limit of normal in 59% (23/39) of the patients and alpha-fetoprotein was less than 40 ng/mL in 97% (38/39) on the completion of treatment. Sustained biochemical response was observed in 53% (19/36) of the patients. In the liver cirrhosis group, serum albumin values and platelet counts increased in 38% (6/16) and 33% (6/18) of patients, respectively. Hepatocellular carcinoma (HCC) appeared in three patients by 13 months after the start of treatment, but no cases were reported thereafter. The cumulative non-carcinogenesis rate of HCC in the liver cirrhosis group was significantly higher in the IFN treatment group compared to the control group (log,rank test, P = 0.046). Conclusion:, Low dose long-term interferon monotherapy to prevent carcinogenesis of HCC was considered useful in aged patients for whom peg-interferon and ribavirin combination therapy is difficult. [source]

Chronic hepatitis C genotype 6 responds better to pegylated interferon and ribavirin combination therapy than genotype 1

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2010
Owen T-Y Tsang
Abstract Background and Aims:, Chronic hepatitis C genotype 6 is common in Hong Kong, especially among i.v. drug abusers. Responses of these patients to combination of pegylated interferon and ribavirin treatment were inconsistent and the numbers of patients involved in previous studies were small. We performed a retrospective study to compare the therapeutic responses of this regimen in patients infected with genotype 6 and genotype 1. Methods:, Seventy patients with either genotype 6 or genotype 1 were recruited. Both groups received 800,1200 mg of ribavirin daily plus either 180 mg of pegylated ,-interferon-2a or 1.5 mg/kg pegylated ,-interferon-2b weekly for 48 weeks. Their responses to treatments were compared. Results:, The early virological response to combination therapy of patients with genotype 6 was significantly better than that of genotype 1 (88.6% vs 74.3%, P = 0.03). Significant difference was also identified in the end of treatment response of the two genotypes (60% vs 81.4% for genotype 1 and 6, respectively; P = 0.005). The sustained virological response (SVR) to treatment in patients with genotype 6 was also significantly superior to that of patients with genotype 1 (75.7% vs 57.1%, P = 0.02). Multiple logistic regression analysis demonstrated that age of 55 years or less, genotypes of hepatitis C virus, liver biopsy staging and baseline hepatitis C virus RNA of 200 000 IU/mL or less were independent predictors for better SVR in this cohort. Conclusion:, Patients with chronic hepatitis C genotype 6 respond better to pegylated interferon and ribavirin combination treatment than patients with genotype 1. [source]

Genotype-specific mechanisms for hepatic steatosis in chronic hepatitis C infection

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2002
Jason M Hui
Abstract Background: Hepatic steatosis is common in hepatitis C, but the relative importance of host and viral factors is controversial. In the present prospective study, we examined metabolic factors associated with non-alcoholic fatty liver and viral genotype as predictors of steatosis and fibrosis in chronic hepatitis C infection. Methods: In 124 chronic hepatitis C patients, the association between liver histology and the following was investigated: demographic and anthropometric data, alcohol intake, alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein,cholesterol, high-density lipoprotein,cholesterol, triglyceride, transferrin saturation, ferritin, insulin, c-peptide, glucose and insulin resistance (homeostasis model). Results: By multivariate analysis, genotype 3 was associated with increased steatosis grade (P = 0.02). There were significant pairwise interactions between genotype 3 status and total cholesterol (P = 0.01), current alcohol intake (P = 0.04) and serum ALT (P = 0.01). This showed that the etiology of steatosis was different in patients with genotype 3 and those with non-genotype 3 chronic hepatitis C infection. In genotype 3 patients, the degree of steatosis was inversely associated with serum cholesterol (P = 0.005) and positively associated with serum triglyceride (P = 0.02). There was no association between body mass index (BMI) and the extent of steatosis. Among patients with other genotypes, the steatosis grade was strongly influenced by BMI (P < 0.0001) and serum ALT (P < 0.01). Independent predictors of fibrosis were age (P = 0.001), past alcohol intake (P = 0.04), ALT (P = 0.002), serum insulin (P = 0.001) and portal inflammation (P < 0.001). Conclusions: Hepatitis C genotype 3 may interfere with pathways of hepatic lipid metabolism, whereas increased BMI appears to be a more important pathogenic factor in other genotypes. Although steatosis and BMI were not associated with hepatic fibrosis, their relationship with serum insulin suggests that metabolic factors related to insulin action could influence fibrogenesis in hepatitis C. [source]

Gene expression profile of transgenic mouse kidney reveals pathogenesis of hepatitis B virus associated nephropathy,

JOURNAL OF MEDICAL VIROLOGY, Issue 5 2006
J. Ren
Abstract Hepatitis B virus (HBV)-associated nephritis has been reported worldwide. Immune complex deposition has been accepted as its pathogenesis, although the association between the presence of local HBV DNA and viral antigen and the development of nephritis remains controversial. To understand better the roles played by HBV protein expression in the kidney, the global gene expression profile was studied in the kidney tissue of a lineage of HBV transgenic mouse (#59). The mice expressed HBsAg in serum, and HBsAg and HBcAg in liver and kidney, but without virus replication. Full-length HBV genome (adr subtype, C genotype) isolated from a chronic HBV carrier was used to establish the transgenic mice #59. Similarly manipulated mice that did not express HBV viral antigens served as controls. Southern blotting, hybridization with HBV probe, and immuno-histochemical staining were used to study HBV gene expression. mRNA extracted from the kidney tissue was analyzed using Affymetrix microarrays. HBsAg and HBcAg were located mainly in the cytoplasm of tubular epithelium. Altogether 520 genes were "up-regulated" more than twofold and 76 genes "down-regulated" more than twofold in the kidney. The complement activation, blood coagulation, and acute-phase response genes were markedly "up-regulated". Compared to the controls, the level of serum C3 protein was decreased in #59 mice, while the level of C3 protein from kidney extract was increased. Results indicate that expression of HBsAg and HBcAg in tubular epithelial cells of the kidney per se can up-regulate complement-mediated inflammatory gene pathways, in addition to immune complex formation. J. Med. Virol. 78:551,560, 2006. © 2006 Wiley-Liss, Inc. [source]

Clinical trial: extended treatment duration of peginterferon-alpha2b plus ribavirin for 72 and 96 weeks in hepatitis C genotype 1-infected late responders

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009
M. NAGAKI
Summary Background, The benefits of prolonging peginterferon and ribavirin after 48 weeks of treatment to maximize sustained virological responses (SVR) in hepatitis C virus (HCV) genotype 1-infected patients remain to be understood. Aim, To investigate whether extended treatment longer than 72 weeks may be superior to 72-week treatment. Methods, A total of 120 treatment-naïve or retreated patients with HCV genotype 1 were treated with peginterferon-alpha-2b (1.5 ,g/kg/week) plus weight-based ribavirin. We had 34 late responders, in whom HCV RNA first became undetectable at week 12,48, and randomized them into three groups receiving standard-dose peginterferon-alpha-2b plus low-dose ribavirin (200 mg/day) for extended 24 weeks (group A), receiving low-dose peginterferon-alpha-2b (0.75 ,g/kg/week) plus low-dose ribavirin for extended 48 weeks (group B) or no extended treatment (group C), and evaluated the outcome according to their virological response. Results, Multivariate analysis showed that the treatment for 96 weeks was identified as a significant, independent factor associated with SVR in HCV genotype 1-infected late responders in comparison with group A [odds ratio (OR), 10.002; P = 0.080] and group C (OR, 17.748; P = 0.025). Conclusion, Extending the treatment duration from 48 weeks to 96 weeks improves SVR rates in genotype 1-infected patients with late virological response to peginterferon-alpha-2b and ribavirin. [source]

Correlation between translation efficiency and outcome of combination therapy in chronic hepatitis C genotype 3

JOURNAL OF VIRAL HEPATITIS, Issue 2 2006
A. Yasmeen
Summary., Combination therapy with interferon- , (IFN- ,) and ribavirin (RBV) in chronic hepatitis C demonstrates the best responses against hepatitis C virus (HCV) of genotype 3. Still, it has proven to be ineffective in 20,30% of patients infected with this genotype. In the present study, we analysed the translation efficiency mediated by the internal ribosome entry site (IRES) region in HCV genotype 3 genomes isolated from sustained responders (SR) and non-responders (NR), assuming that this may influence the outcome of treatment. Pretreatment isolates of genotype 3 from 22 individuals (15 SR, seven NR) were selected for such analyses. The IRES region [nucleotide (nt) 1,407] was cloned into a dual luciferase vector and IRES activity assessed following transfection into various cell lines. Low relative translation efficiency was observed for IRES elements derived from SR patients, whereas those of NR patients showed significantly greater translation efficiency (29.7 ± 13 vs 69.4 ± 22; P < 0.01). Subsequently, the effect of IFN- , plus RBV on IRES-driven translation in vitro was determined. A greater suppressive effect was observed on IRES activity isolated from seven SR patients, when compared with seven NR patients. In conclusion, IRES efficiency in vitro correlated with treatment response for HCV genotype 3. Further studies are warranted to investigate whether IRES efficiency in vitro, or sequence motifs associated with IRES efficiency, will be worthwhile to explore as prognostic tools for other HCV genotypes in the treatment of chronic HCV infection. [source]

Interleukin-6 involvement in brain arteriovenous malformations

ANNALS OF NEUROLOGY, Issue 1 2006
Yongmei Chen MD
We recently reported that the GG genotype of the interleukin-6 (IL-6),174G>C promoter polymorphism is associated with clinical presentation of intracranial hemorrhage in brain arteriovenous malformation (AVM) patients. In this study, we investigated whether tissue IL-6 expression was associated with IL-6,174G>C genotype, and whether IL-6 was linked to downstream targets involved in angiogenesis and vascular instability. Our results showed that the highest IL-6 protein levels in brain AVM tissue were associated with IL-6,174GG genotype (GG: 57.7 ± 20.2; GC: 35.6 ± 26.6; CC: 13.9 ± 10.2pg/mg; p = 0.001). IL-6 protein levels were increased in AVM tissue from patients with hemorrhagic presentation compared with patients without hemorrhage (55 ± 22 vs 40 ± 27pg/mg; p = 0.038). IL-6 messenger RNA expression strongly correlated with messenger RNA levels of IL-1,, tumor necrosis factor-,, IL-8, matrix metalloproteinase-3 (MMP-3), MMP-9, and MMP-12. We further investigated the plausibility of IL-6 being an upstream cytokine responsible for initiating the angiogenic cascade by cell culture and animal experiments. IL-6 induced MMP-3 and MMP-9 expression and activity in mouse brain and increased proliferation and migration of cerebral endothelial cells. Together, our results suggest that the IL-6 genotype associated with intracranial hemorrhage modulates IL-6 expression in brain AVM tissue, which is consistent with the hypothesis that inflammatory processes induce angiogenic activity possibly contributory to brain AVM intracranial hemorrhage. Ann Neurol 2005 [source]

Distribution of HLA-A, B alleles and polymorphisms of TAP and LMP genes in Korean patients with atopic dermatitis

CLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2001
H. J. Lee
Background Atopic dermatitis has been seen to result from multifactorial inheritance, with interaction between genetic and environmental factors. The genetic association may differ according to the ethnic backgrounds. Objective The purpose of this study was to investigate the genetic factors in Korean atopic dermatitis patients by studying the human leucocyte antigen (HLA) class I association and polymorphisms of transporters associated with antigen presentation (TAP) and low-molecular-weight polypeptide (LMP) genes. Methods HLA-A and B genotyping was performed in 53 atopic dermatitis patients and 184 healthy controls using the standard microlymphocytotoxicity technique. TAP1, TAP2, LMP2, and LMP7 gene polymorphisms were anaylzed using the polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP), PCR-amplification refractory mutation system (ARMS), and PCR-restriction fragment length polymorphism (RFLP). Results Allele frequency of HLA-A24 was significantly increased in patients with atopic dermatitis compared to controls (P < 0.05). HLA-B alleles showed no differences in distribution between patients and controls. Genotype, phenotype, and allele frequencies of TAP1 gene also revealed no differences in distribution between patients and controls. Analysis of TAP2 gene polymorphisms showed increased frequencies of the TAP2*C allele and TAP2*A/TAP2*C genotype in atopic dermatitis patients compared to controls (P < 0.05). Distribution of LMP2 and LMP7 gene polymorphisms was similar for patients and controls. Conclusion This study demonstrates an association of atopic dermatitis with HLA-A24 and TAP2*C alleles in Korean patients. Discrepancy with the previous reports might be related to different patient characteristics and ethnic variations. [source]

Response to pegylated interferon and ribavirin in Asian American patients with Chronic hepatitis C genotypes 1 vs 2/3 vs 6

JOURNAL OF VIRAL HEPATITIS, Issue 10 2010
N. H. Nguyen
Summary., Chronic hepatitis C is generally underappreciated in Asian Americans, and most pivotal studies were conducted in western countries and only included a small numbers of Asian patients. Our goal was to examine and compare treatment outcomes in these patients with genotypes 1 vs 2/3 vs 6. We performed a retrospective cohort study of 167 consecutive treatment-naïve Asian American patients treated with pegylated interferon (PEG IFN) plus ribavirin (RBV) at two community clinics in Northern California from 12/00 to 1/08. Primary outcome was sustained virological response rate by intention-to-treat analysis. The overall completion rate was 76%, and treatment adherence (completion of ,75,80% PEG IFN + RBV dose for ,75,80% of intended duration) was 74%. Significant depression was noted in only 4% of patients. Sustained virologic response in patients with genotype 6 treated for 48 weeks was similar to that seen in those with genotype 2/3 (74%vs 75%, P = 0.89) and significantly higher than those with genotype 1 (74%vs 49%, P = 0.016). On multivariate analysis inclusive of sex, age, body mass index (,25 vs >25) and viral load, only treatment adherence and genotype (2/3 and 6 treated for 48 weeks) were found to be significant predictors of sustained virologic response. We conclude that significant depression is rare in Asian American patients (4%). Patients with genotype 6 treated for 48 weeks appear to have a similar treatment response rate as patients with genotype 2/3 and a significantly higher response rate than those with genotype 1. [source]

Polymorphisms in the interleukin-1 gene influence the stratum corneum interleukin-1, concentration in uninvolved skin of patients with chronic irritant contact dermatitis

CONTACT DERMATITIS, Issue 5 2008
Cindy M. DeJongh
Background:, Interleukin (IL)-1, and its receptor antagonist IL-1ra play a role in skin inflammation. Several polymorphisms in the IL1 gene cluster, coding for IL-1,, IL-1ra, and IL-1,, influence their protein expression. Within this cluster, strong linkage disequilibrium has been shown. Objective:, We studied the association between the polymorphisms IL1A -889 (C,T) and IL1B -31 (T,C) and the concentration of IL-1, and IL-1ra in the stratum corneum (SC). Method:, In 124 patients with chronic irritant contact dermatitis, we genotyped the IL1A -889 and IL1B -31 polymorphisms and determined the amount of IL-1, and IL-1ra on tape strips obtained from uninvolved skin of the volar forearm. Results:, The SC IL-1, concentration was 23% and 47% lower in subjects with IL1A -889 C/T genotype and T/T genotype, respectively, compared with wild-type genotype. In subjects with IL1B -31 C/C genotype, the IL-1, concentration was 51% lower compared with C/T and T/T genotypes. The ratio IL-1ra/IL-1, increased twofold in IL1A -889 C/T genotype and threefold in T/T genotype compared with wild type. Conclusions:, We have shown a clear effect of IL1 genotype on protein expression in the SC. This altered expression may be responsible for the interindividual differences in the inflammatory response of the skin. [source]

Vascular endothelial growth factor gene polymorphisms are associated with the risk of developing adenomyosis

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 5 2009
Shan Kang
Abstract Vascular endothelial growth factor (VEGF), a major mediator of angiogenesis and vascular permeability, may play a key role in the development of adenomyosis. The aim of this study was to investigate whether these four VEGF polymorphisms (,2578C/A, ,1154G/A, ,460C/T, and +936C/T) were associated with the risk of adenomyosis development. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 174 adenomyosis patients and 199 frequency-matched control women. There were significant differences between patients and control group in allele frequencies and genotype distributions of the ,2578C/A polymorphisms (P = 0.010 and 0.044, respectively). Compared with the C/C genotype, the A/A + C/A genotype could significantly modify the risk of developing adenomyosis [odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.42,0.97]. For the ,1154G/A polymorphism, the allele frequencies and genotype distributions in patient group were significant different from those of the controls (P = 0.001 and 0.007, respectively). Compared with the G/G genotype, the A/A + G/A genotype could significantly decrease the risk of developing adenomyosis (OR = 0.51, 95% CI = 0.33,0.80). However, the genotype distributions and allele frequencies of the ,460C/T and +936C/T polymorphisms did not significantly differ between controls and patients (all P value > 0.05). The haplotype analysis suggested that the TGA (VEGF ,460/,1154/,2578) and CGA haplotypes exhibited a significant decrease in the risk of developing adenomyosis compared with the haplotype of TGC (OR = 0.64, 95% CI = 0.41,1.00; OR = 0.44, 95% CI = 0.21,0.93, respectively). The study indicated that the ,2578A or ,1154A allele of VEGF gene could significantly decrease the risk of adenomyosis and might be potentially protective factors for adenomyosis development. Environ. Mol. Mutagen., 2009. © 2009 Wiley-Liss, Inc. [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]

Association of the VDR Translation Start Site Polymorphism and Fracture Risk in Older Women,,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2007
Susan P Moffett PhD
Abstract We evaluated the association between the VDR translation start site polymorphism and osteoporotic phenotypes among 6698 older white women. Women with the C/C genotype had lower wrist BMD and an increased risk of wrist and all non-spine/low-trauma fractures. The high frequency of this variant confers a population attributable risk that is similar to several established risk factors for fracture. Introduction: The vitamin D receptor (VDR) is a nuclear receptor that regulates bone formation, bone resorption, and calcium homeostasis. A common C to T polymorphism in exon 2 of the VDR gene introduces a new translation start site and a protein that differs in length by three amino acids (T = 427aa, C = 424aa; rs10735810). Materials and Methods: We conducted genetic association analyses of this polymorphism, BMD, and fracture outcomes in a prospective cohort of 6698 white American women ,65 years of age. Incident fractures were confirmed by physician adjudication of radiology reports. There were 2532 incident nontraumatic/nonvertebral fractures during 13.6 yr of follow-up including 509 wrist and 703 hip fractures. Results: Women with the C/C genotype had somewhat lower distal radius BMD compared with those with the T/T genotype (CC = 0.358 g/cm2, CT = 0.361 g/cm2, TT = 0.369 g/cm2, p = 0.003). The C/C genotype was also associated with increased risk of non-spine, low traumatic fractures (HR: 1.18; 95% CI: 1.04, 1.33) and wrist fractures (HR: 1.33; 95% CI: 1.01, 1.75) compared with the T/T genotype in age-adjusted models. Further adjustments for distal radius BMD only slightly attenuated these associations. The VDR polymorphism was not associated with hip fracture. The population attributable risk (PAR) of the C/C genotype for incident fractures was 6.1%. The PAR for established risk factors for fracture were: low femoral neck BMD (PAR = 16.3%), maternal history of fracture (PAR = 5.1%), low body weight (PAR = 5.3%), corticosteroid use (PAR = 1.3%), and smoking (PAR = 1.6%). Similar PAR results were observed for wrist fractures. Conclusions: The common and potentially functional VDR translation start site polymorphism confers a modestly increased relative risk of fracture among older white women. However, the high frequency of this variant confers a population attributable risk that is similar to or greater than several established risk factors for fracture. [source]

Genetic,morphologic association study: association between the low density lipoprotein-receptor related protein (LRP) and cerebral amyloid angiopathy

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 1 2005
M. Christoforidis
Accumulating evidence suggests that genetic factors such as apolipoprotein E (APOE), can act in different ways in the pathogenesis of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). The role of the low-density lipoprotein-receptor related protein (LRP), the major cerebral APOE receptor, in AD has been discussed controversially depending on data from different populations and methodological approaches. We examined the influence of LRP polymorphisms on CAA in 125 post-mortem cases genotyped for APOE and classified according to the neurofibrillary Braak and Braak staging of AD (indicating neurodegeneration grade). CAA was assessed separately for leptomeningeal (CAAlep.), noncapillary cortical (CAAcort.) and capillary cortical (CAAcap.) vessels in ,-amyloid stained sections. Our results suggest: (i) the 87 bp allele of LRP5, polymorphism (LRP5,) is an independent predictive factor for CAAcort. and CAAlep.; (ii) the C/C genotype (C allele) of the LRP exon 3 polymorphism is positively associated with, the, severity, of, CAAlep., and, CAAcort.,, implicating a younger age of CAA onset and/or faster CAA progression; (iii) as CAAcort. and CAAlep. showed different genetic associations in contrast to CAAcap., we can underscore the hypothesis that different molecular mechanisms are involved in CAA pathogenesis of noncapillary and capillary cerebral vessels. Our results lead us to postulate that the LRP5,87 bp and the LRP exon 3 C alleles of the LRP gene (or another locus that might be in linkage disequilibrium with these LRP polymorphic sites) could modify cerebrovascular LRP function or expression in noncapillary cerebral vessels, leading to an increased cerebrovascular amyloid deposition. [source]

SHORT COMMUNICATION: STAT3 Polymorphisms Linked with Idiopathic Recurrent Miscarriages

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010
Ramzi R. Finan
Problem, We investigated the association of signal transducers and activators of transcription (STAT)3 gene variants with idiopathic recurrent miscarriage (RM). Method of Study, A case,control study involving 189 RM patients and 244 control women was carried out. STAT3 (rs1053004 and rs1023023) genotyping was performed by allelic discrimination/real-time PCR method. Results,STAT3 rs1053004 C allele [OR (95% CI) = 1.60 (1.22,2.10)] and C/C genotype [OR (95% CI) = 3.42 (1.70,6.92)] were positively associated with RM. Two-locus (rs1053004/rs1053023) haplotype analysis revealed increased frequency of CG and CA haplotypes in RM patients, of which only CA haplotype (Pc = 0.020) remained positively associated with RM after applying the Bonferroni correction. This was confirmed by multivariate regression analysis (OR = 1.70; 95% CI = 1.17,2.46) after adjusting for a number of covariates. Conclusion,STAT3 rs1053004 variant is significantly associated with idiopathic RM. Replication studies on other racial groups and other STAT3 gene variants are warranted. [source]

SERPINE1 intron polymorphisms affecting gene expression are associated with diffuse-type gastric cancer susceptibility

CANCER, Issue 18 2010
Hyoungseok Ju PhD
Abstract BACKGROUND: A primary inhibitor of plasminogen activators, SERPINE1 (serpin peptidase inhibitor 1, clade E, member 1, also known as plasminogen activator inhibitor type 1), is an important regulator in tumorigenesis and is highly expressed in many cancers. METHODS: Five tag single nucleotide polymorphisms (SNPs) and 1 insertion polymorphism within SERPINE1 were genotyped in 1101 unrelated Korean individuals (a case group of 612 patients with gastric cancer and a control group of 489 healthy individuals). Associations with susceptibility to diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer were assessed using multivariate logistic regression analyses adjusted for age and sex. Allelic differences in the contribution to gene expression were measured using luciferase assays. RESULTS: SNP c.1162+162C>T (rs2227692) in intron 7 was associated with susceptibility to DGC but not with susceptibility to intestinal-type gastric cancer. The minor allele-carrying genotypes C/T and T/T had 1.6-fold greater odds of DGC than the C/C genotype (P = .00084). This SNP was linked to a repeat-number variation c.1162+604AAAG(11_17), a deletion (del) variation c.1162+664_1162+673del, and another SNP c.1162+859T>A (rs2070683) in intron 7 based on the sequencing of 5 patients and 5 controls. The risk haplotype of the 4 variations exhibited a 30% greater gene expression level than the nonrisk haplotype in luciferase reporter assays (P = .025). In contrast, DGC susceptibility was not associated with the c.,1969_,1968insG polymorphism (rs1799768) in the promoter, commonly known as 4G/5G, in which the minor 5G allele is less active in transcription than the major 4G allele. CONCLUSIONS: An association between SERPINE1 and DGC susceptibility was observed with 4 correlated polymorphisms in intron 7 rather than the 4G/5G polymorphism in the promoter, although all polymorphisms affected gene expression. Cancer 2010. © 2010 American Cancer Society. [source]

Interleukin 1 Polymorphisms, Lifestyle Factors, and Helicobacter pylori Infection

CANCER SCIENCE, Issue 4 2001
Nobuyuki Hamajima
Associations between Helicobacter pylori (HP) infection and lifestyle factors have been reported by several authors, but little is known about the host factors associated with the infection. This study aims to examine the infection rate of HP according to gene polymorphisms of interleukin (TL)-IA, IL-1B, and IL-1RN, and to investigate the interactions with lifestyle factors. Subjects were 241 non-cancer outpatients who had participated in a HP eradication program. Polymorphisms at -889 (T to C) of IL-1A, at -31 (C to T; T allele makes a TATA box) and -511 (C to T) of IL-1B, and at intron 2 (86-bp VNTR (variable number of tandem repeats)) of IL-1RN were genotyped by PCR (polymerase chain reaction), PCR-RFLP (restriction fragment length polymorphism) and PCR-CTPP (PCR with confronting two-pair primers). It was found that IL-1B polymorphisms at -31 and -511 were near-completely linked, but in the opposite way to that in Caucasians; -31C/ -511T and -31T/-511C alleles were dominant in the present subjects. The HP infection rate was substantially different among the genotypes of IL-1B C-31T; 45.2% (19/42) for the C/C, 67.7% (90/133) for the C/T, and 63.6% (42/66) for the T/T. The age-sex adjusted odds ratio (OR) relative to the C/C genotype was 2.32 (95%CI (confidence interval), 1.10-4.92) for the T/C genotype and 2.46 (1.06-5.74) for the T/T genotype. The OR for the T/T genotype was significantly modified by smoking status; interaction term=14.6 (1.12-190). The polymorphisms of IL-1A and IL-1RN were not associated with the infection rate. The results suggested that the T allele of IL-1B C-31T is associated with vulnerability to persistent HP infection, and that the vulnerability is modified by smoking. [source]

Interleukin-1, and -10 polymorphisms influence erosive reflux esophagitis and gastritis in Taiwanese patients

Low plasma adiponectin concentration is associated with myocardial infarction in young individuals

JOURNAL OF INTERNAL MEDICINE, Issue 2 2010
J. Persson
Abstract., Persson J, Lindberg K, Gustafsson TP, Eriksson P, Paulsson-Berne G, Lundman P. (Danderyd University Hospital; Karolinska Institutet, Novum; Karolinska University Hospital, Karolinska Institutet; Atherosclerosis Research Unit; Karolinska Institutet, Stockholm, Sweden). Low plasma adiponectin concentration is associated with myocardial infarction in young individuals. J Intern Med 2010; 268: 194,205. Objective., The importance of adiponectin in coronary heart disease remains to be elucidated. Therefore, the associations between plasma adiponectin levels and i) myocardial infarction and ii) genetic variation within the adiponectin gene were investigated. Methods., The study included young survivors (age <60 years) of a first myocardial infarction and gender- and age-matched controls (244 pairs). Adiponectin concentrations were analysed by radioimmunoassay. Two polymorphisms, rs266729 and rs1501299, of the adiponectin gene ADIPOQ were genotyped. Results., Adiponectin levels were inversely associated with myocardial infarction [odds ratio (OR) 9.3, 95% confidence interval (CI) 4.7,18.2, for the lowest quartile compared to the highest quartile]. This persisted after adjustment for history of hypertension, HDL cholesterol, smoking and body mass index (BMI) (OR 3.1, 95% CI 1.3,7.6). The rs266729 polymorphism was associated with adiponectin levels. Plasma adiponectin concentrations were lower in individuals with the rare G/G genotype [median 4.3 mg mL,1, interquartile range (IQR) 2.8,6.2] compared to the C/G (median 5.8 mg mL,1, IQR 3.9,8.0; P = 0.035) and C/C genotypes (median 5.5 mg mL,1, IQR 4.0,7.5; P = 0.083). Conclusion., Low plasma adiponectin concentrations are associated with myocardial infarction in individuals below the age of 60, and this remains significant after adjustment for history of hypertension, HDL cholesterol, smoking and BMI. In addition, adiponectin levels differ according to rs266729 genotype. [source]

Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at-risk Italian population

INTERNATIONAL JOURNAL OF CANCER, Issue 3 2006
Francesco Graziano
Abstract We performed a case-control study to examine the relationship between MTHFR C677T gene polymorphism (MTHFR677C/T) and gastric cancer susceptibility in at-risk populations in central Italy. To explore genomic DNA hypomethylation as a potential etiologic mechanism, this phenomenon was evaluated in carriers of the MTHFR677T/T genotype and carriers of the wild-type MTHFR677C/C genotype. Lymphocyte genomic DNA from 162 gastric cancer patients and 164 controls was used for MTHFR677C/T genotyping. Unconditional regression analysis with ORs and 95% CIs was used to investigate the association of the polymorphism with disease. Genomic DNA methylation status by an established enzymatic assay that measures the DNA accepting capacity of methyl groups (inversely related to endogenous methylation) was assessed in a random sample of 40 carriers of the wild-type MTHFR677C/C genotype and 40 carriers of the MTHFR677T/T genotype. The global allelic distribution was in Hardy-Weinberg equilibrium. The MTHFR677T allele was significantly associated with gastric cancer risk with an OR of 2.49 (95% CI 1.48,4.20) in heterozygous MTHFR677C/T carriers and an OR of 2.85 (95% CI 1.52,5.35) in homozygous MTHFR677T/T carriers. This risk association was retained in subgroup analyses by tumor histotype and location. Genomic DNA hypomethylation status in MTHFR677T/T carriers was significantly higher than in subjects with wild-type MTHF677C/C genotype (p = 0.012). In the studied population, MTHFR677T played the role of a moderate-penetrance gastric cancer susceptibility allele. Possession of the MTHFR677T/T genotype was significantly associated with genomic DNA hypomethylation. These findings deserve further investigation in the context of novel strategies for gastric cancer prevention. © 2005 Wiley-Liss, Inc. [source]