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Caucasian Subjects (caucasian + subject)
Selected AbstractsEthnic differences in plantar pressures in diabetic patients with peripheral neuropathyDIABETIC MEDICINE, Issue 4 2008M. P. Solano Abstract Aims To compare plantar foot pressures between Caucasian and Hispanic diabetic patients with peripheral neuropathy (PN) without a history of foot ulceration and between Caucasian and Hispanic non-diabetic individuals. Methods Forty-four Hispanic diabetic patients with PN (HDPN), 35 Caucasian diabetic patients with PN (CDPN), 41 non-diabetic Hispanic subjects and 33 non-diabetic Caucasian subjects participated. Total and regional peak plantar pressures (PPs) and pressure time integrals (PTIs) were assessed using the EMED-SF-4 plantar pressure system. Results Hispanic diabetic patients with PN had significantly lower peak PP than Caucasian diabetic patients with PN in the entire foot (552.4 ± 227.9 vs. 810.1 ± 274.6 kPa; P < 0.001), forefoot (464.1 ± 222.6 vs. 699.6 ± 323.1 kPa; P < 0.001), hindfoot (296.3.4 + 101.8 vs. 398.1 + 178.3 kPa; P < 0.01) and at the fifth metatarsal head (MTH5; 204.3 ± 143.2 vs. 388.2 ± 273.9 kPa; P < 0.001). The PTI in the entire foot, forefoot and MTH5 were also lower in HDPN than in CDPN. The ethnic differences between the diabetic groups with PN for the entire foot, forefoot and MTH5 remained significant after adjusting for the effect of age, gender, weight and duration of diabetes. There were no significant differences in peak PP and PTI among non-diabetic individuals, except for a lower peak PP at the MTH5 in Hispanic compared with Caucasian subjects. Conclusions Despite a well-known higher incidence of foot complications in diabetic Hispanic subjects, dynamic plantar pressures are lower in Hispanic diabetic patients with PN when compared with their Caucasian counterparts, suggesting that differences in other risk factors exist between these two ethnic groups. [source] Pharmacokinetics of carisbamate (RWJ-333369) in healthy Japanese and Western subjectsEPILEPSIA, Issue 8 2009Peter Zannikos Summary Purpose:, To compare the pharmacokinetics of carisbamate (RWJ-333369) in healthy Japanese and Western adults, and to comparatively assess carisbamate safety and tolerability between the two populations. Methods:, An open-label study was conducted in 24 Japanese and 24 Caucasian healthy subjects. Subjects received a single oral dose of 250 mg carisbamate on day 1 followed by a 3-day washout period; twice-daily dosing of 250 mg carisbamate on days 5,8; subsequently, 500 mg on days 9,12 and a single dose of 500 mg on day 13. Plasma samples were collected for a pharmacokinetic analysis on days 1, 8, and 13. Plasma and urine samples were analyzed for carisbamate and its urinary metabolites by liquid-chromatography-mass-spectrometry. Results:, Following a single dose, carisbamate Cmax and area under the curve (AUC) geometric mean ratios were 16.4% and 28.8% higher in Japanese than in Caucasians, respectively; these differences were statistically significant and their 90% confidence intervals (CIs) fell outside of the 80,125% limits, which are considered not to be of clinical significance. With dose,body weight normalization, Cmax and AUC were similar in Japanese and Caucasian subjects and the 90% CIs were within the 80,125% boundaries. Carisbamate was well tolerated, and its mean oral clearance and half-life were similar in both groups, ranging from 35.1,41.4 ml/h/kg and 11.5,12.8 h. Discussion:, Carisbamate plasma exposure (AUC) and Cmax in Japanese subjects is ,20,25% higher than in Caucasians due to a higher mg/kg dose. After body weight normalization, carisbamate pharmacokinetics was similar between Japanese and Caucasian subjects following single and multiple dosing, and showed the same dose proportionality. [source] Genetic variants in the IMPA2 gene do not confer increased risk of febrile seizures in Caucasian patientsEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2007M. A. Blair Pathogenesis of febrile seizures (FS), causing the most common of types of seizures in children, remains unknown. Genetic factors appear to play a pivotal role and FS can be inherited as a monogenic or genetically complex disorder. Several risks factors have been proposed but many of the previously reported genetic associations were not replicated. Non-coding polymorphisms in the myo-inositol monophosphatase 2 gene (IMPA2) have been suggested as a susceptibility factor for FS in Japanese patients. It is unknown whether genetic variants in the same gene constitute a risk factor for FS in other ethnic groups because the frequency of FS is significantly higher in Japanese children than in Caucasian patients. We investigated the role of the IMPA2 gene in a cohort of 96 unrelated Caucasian subjects with a history of FS. We did not identify any significant differences in genotypes of cases and matched controls; no mutations or non-synonymous polymorphisms were detected in these individuals. Our data suggest that the genetic variants in the IMPA2 gene are not associated with a risk of FS in Caucasian patients and patients from various genetic groups are likely to have different genetic causes of FS. [source] Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver,HEPATOLOGY, Issue 4 2009Anne T. Nies An important function of hepatocytes is the biotransformation and elimination of various drugs, many of which are organic cations and are taken up by organic cation transporters (OCTs) of the solute carrier family 22 (SLC22). Because interindividual variability of OCT expression may affect response to cationic drugs such as metformin, we systematically investigated genetic and nongenetic factors of OCT1/SLC22A1 and OCT3/SLC22A3 expression in human liver. OCT1 and OCT3 expression (messenger RNA [mRNA], protein) was analyzed in liver tissue samples from 150 Caucasian subjects. Hepatic OCTs were localized by way of immunofluorescence microscopy. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and genome-wide single-nucleotide polymorphism microarray technology served to genotype 92 variants in the SLC22A1-A3/OCT1-3 gene cluster. Transport of metformin by recombinant human OCT1 and OCT3 was compared using transfected cells. OCT1 mRNA and protein expression varied 113- and 83-fold, respectively; OCT3 mRNA expression varied 27-fold. OCT1 transcript levels were on average 15-fold higher compared with OCT3. We localized the OCT3 protein to the basolateral hepatocyte membrane and identified metformin as an OCT3 substrate. OCT1 and OCT3 expression are independent of age and sex but were significantly reduced in liver donors diagnosed as cholestatic (P , 0.01). Several haplotypes for OCT1 and OCT3 were identified. Multivariate analysis adjusted for multiple testing showed that only the OCT1-Arg61Cys variant (rs12208357) strongly correlated with decreased OCT1 protein expression (P < 0.0001), and four variants in OCT3 (rs2292334, rs2048327, rs1810126, rs3088442) were associated with reduced OCT3 mRNA levels (P = 0.03). Conclusion: We identified cholestasis and genetic variants as critical determinants for considerable interindividual variability of hepatic OCT1 and OCT3 expression. This indicates consequences for hepatic elimination of and response to OCT substrates such as metformin. (HEPATOLOGY 2009.) [source] Metabolic differences between Asian and Caucasian patients on clozapine treatmentHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2007Mythily Subramaniam Abstract Objective To establish if there are ethnic differences in the various metabolic disturbances that are common with clozapine treatment. Method Forty subjects (20 Asians and 20 Caucasians) with a diagnosis of schizophrenia were recruited for the study. Clozapine blood levels as well as fasting blood glucose, lipid levels, and liver function tests were established. Other clinical parameters such as blood pressure and Body Mass Index (BMI) were recorded for each patient. Results The mean clozapine dose was significantly higher in the Caucasian subjects (432.5,±,194.7,mg) as compared to the Asian subjects (175.6,±,106.9,mg) (p,<,0.001) while the mean weight-corrected dose for Asian patients was lower (3.0,±,1.9 and 5.0,±,2.1,mg/kg, respectively, p,=,0.005). There were, however, no ethnic differences in the mean plasma clozapine concentration (415.3,±,185.8,ng/ml in Caucasians and 417.1,±,290.8,ng/ml in Asians). BMI were significantly higher in Caucasians, as were the number of subjects with hypertension; levels of hepatic enzymes were higher in the Asian group. Conclusions Not only are there pharmacokinetic differences between Asian and Caucasian patients receiving clozapine, but there may also be differential emergence of certain metabolic abnormalities like hypertension and weight gain in these two ethnic groups. However, the effects of life style including diet and exercise cannot be excluded. Copyright © 2007 John Wiley & Sons, Ltd. [source] Single-Nucleotide Polymorphisms in Corticotropin Releasing Hormone Receptor 1 Gene (CRHR1) Are Associated With Quantitative Trait of Event-Related Potential and Alcohol DependenceALCOHOLISM, Issue 6 2010Andrew C. H. Chen Background:, Endophenotypes reflect more proximal effects of genes than diagnostic categories, hence providing a more powerful strategy in searching for genes involved in complex psychiatric disorders. There is strong evidence suggesting the P3 amplitude of the event-related potential (ERP) as an endophenotype for the risk of alcoholism and other disinhibitory disorders. Recent studies demonstrated a crucial role of corticotropin releasing hormone receptor 1 (CRHR1) in the environmental stress response and ethanol self-administration in animal models. The aim of the present study was to test the potential associations between single-nucleotide polymorphisms (SNPs) in the CRHR1 gene and the quantitative trait, P3 amplitude during the processing of visual target signals in an oddball paradigm, as well as alcohol dependence diagnosis. Methods:, We analyzed a sample from the Collaborative Study on the Genetics of Alcoholism (COGA) comprising 1049 Caucasian subjects from 209 families (including 472 alcohol-dependent individuals). Quantitative transmission disequilibrium test (QTDT) and family-based association test (FBAT) were used to test the association, and false discovery rate (FDR) was applied to correct for multiple comparisons. Results:, Significant associations (p < 0.05) were found between the P3 amplitude and alcohol dependence with multiple SNPs in the CRHR1 gene. Conclusions:, Our results suggest that CRHR1 may be involved in modulating the P3 component of the ERP during information processing and in vulnerability to alcoholism. These findings underscore the utility of electrophysiology and the endophenotype approach in the genetic study of psychiatric disorders. [source] Clinical evaluation of a single-wavelength fractional laser and a novel multi-wavelength fractional laser in the treatment of photodamaged skin,LASERS IN SURGERY AND MEDICINE, Issue 6 2009Laurel Naversen Geraghty BA Abstract Background and Objectives Nonablative fractional lasers are well recognized for rejuvenating photoaged skin. We previously reported favorable outcomes with short follow-up after the use of 1,440-nm Nd:YAG laser energy used alone or in combination with a 1,320-nm laser to effect rejuvenation and wrinkle reduction. We now report longer follow-up data. Study Design/Materials and Methods Nineteen Caucasian subjects (average age 47±8.4; range 33,62) exhibiting mild-to-moderate photoaging of the face and neck were treated four times (average interval 18.1± 4.1 days; range 11,37 days) with the 1,440-nm Nd:YAG fractional laser (average fluence 3.7±0.3,J/cm2) or the 1,320/1,440-nm multiplex Nd:YAG fractional laser (1,320-nm average fluence 8.4±0.4,J/cm2; 1,440-nm average fluence 2.3±0.2,J/cm2). Outcomes were assessed by subjects and the treating physician using a quartile scale to evaluate skin tightening, surface texture, rhytids, dyschromia, erythema, and global appearance after 1, 3, and 6 months. Retroauricular punch biopsies from three patients were used to evaluate wound healing. Three patients withdrew from the study prior to evaluation, one missed the 1-month evaluation, and one missed the 6-month evaluation. Results Assessment by subjects and the treating physician revealed clinical improvement for all outcomes after 1, 3, and 6 months. The differences between the treatment groups were not statistically significant. Subjects demonstrated the greatest average 6-month improvements in surface texture and global skin appearance. Subjects treated with the multiplex laser reported more skin tightening than the group treated only with the 1,440-nm laser. Histological evaluation revealed wound healing within 10 days and significant neocollagenesis at 3 months. No adverse events were reported in any subject. Conclusion The 1,440-nm Nd:YAG and 1,320/1,440-nm multiplex Nd:YAG lasers safely and effectively produced improved surface texture, rhytids, dyschromia, erythema, global skin appearance, and skin tightening. Histopathologic findings correlated with clinical observations. Lasers Surg. Med. 41:408,426, 2009. © 2009 Wiley-Liss, Inc. [source] A pilot study on the differences in wavefront aberrations between two ethnic groups of young generally myopic subjectsOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 6 2008Alejandro Cerviño Abstract A comparative population-based cross-sectional study design was used to examine the prevalence of wavefront patterns in two different ethnic groups, and the relationship of these patterns with ocular biometrics and gender. The Shin,Nippon SRW5000 open field autorefractor, the Wavefront Analysis Supported Customized Ablation (WASCA) wavefront analyser and the IOLMaster were used to determine wavefront aberrations, mean spherical equivalent (SE) refractive error and axial length (AL). Seventy-four eyes from 74 young healthy subjects (44 British Asians, 30 Caucasians; 36 men, 38 women; mean age 22.51 ± 3.89 years) with mean SE averaging ,1.90 ± 2.76 D (range ,10.88 to +2.19 D) were examined. Relationships between ethnicity, gender, AL and SE, against the wavefront high-order root mean square, and aberration components up to the fifth order, were assessed by using multiple regression and correlation analysis. AL on its own accounted for 4.7% of the variance in trefoil component (F1,72 = 4.602; p = 0.035), 13.7% of coma component (F1,72 = 12.536; p = 0.001), 6.1% of trefoil component (F1,72 = 5.705; p = 0.020) and 9.8% of coefficient (F1,72 = 8.908; p = 0.004). A significant model emerged (F2,71 = 6.164; p = 0.003) for ethnicity and axial length, accounting for 12.4% of variance in primary spherical aberration with ethnicity accounting for 8.4% of that variance. For Caucasian subjects, a significant correlation was found between axial length and (Pearson's correlation coefficient ,0.500; p = 0.005) and (Pearson's correlation coefficient ,0.423; p = 0.020). For British Asian subjects, AL was only correlated with coefficient (Pearson's correlation coefficient ,0.358; p = 0.017). Ethnicity is a factor to be considered in the variability of wavefront aberration, particularly spherical aberration. Relationship between AL and wavefront aberrations seems to vary between ethnicities. If higher order aberrations play a role in the emmetropization process, this may be different for different populations. [source] Adolescent Health Behaviors and Related Factors: A ReviewPUBLIC HEALTH NURSING, Issue 2 2001Hila J. Spear R.N., Ph.D. This review examined research relevant to adolescent health behavior in order to identify key behaviors and factors related to behaviors for targeting health-promoting interventions. The 34 studies reviewed sampled mainly Caucasian subjects ranging in age from 12 to 24 years. The majority of the studies were descriptive and cross-sectional, and they dealt with a specific health behavior or group of behaviors such as eating, sleeping, and exercise. Primary factors related to health behavior included gender, family structure, ethnicity, knowledge, and attitudes. Increased knowledge of factors that impact adolescent health behaviors is essential so that public health nurses (PHNs) and other health professionals can be more responsive to developmental and lifestyle factors influencing the health of youth within families and communities. [source] Analysis of Single Nucleotide Polymorphisms in the NOS2A Gene and Interaction with Smoking in Age-Related Macular DegenerationANNALS OF HUMAN GENETICS, Issue 3 2010Juan A. Ayala-Haedo Summary Age-related macular degeneration (AMD) is a complex degenerative retinal disease influenced by both genetic and environmental risk factors. We assessed whether single nucleotide polymorphisms (SNPs) in the NOS2A gene increase risk and modulate the effect of smoking in AMD. 998 Caucasian subjects (712 AMD cases and 286 controls) were genotyped for 17 SNPs in NOS2A. Multivariable logistic regression models containing SNP genotypes, age, sex, smoking status and genotype/smoking interaction were constructed. SNP rs8072199 was significantly associated with AMD (OR = 1.3; 95% CI : 1.02, 1.65; P= 0.035). A significant interaction with smoking was detected at rs2248814 (P= 0.037). Stratified data by genotypes demonstrated that the association between AMD and smoking was stronger in carriers of AA genotypes (OR = 35.98; 95% CI: 3.19, 405.98) than in carriers of the AG genotype (OR = 3.05; 95% CI: 1.36, 6.74) or GG genotype (OR = 2.1; 95% CI: 0.91, 4.84). The results suggest a possible synergistic interaction of AA genotype with smoking, although the result bears replication in larger samples. Our data suggests that SNPs in the NOS2A gene are associated with increased risk for AMD and might modulate the effect of smoking on AMD. [source] Genome-Wide Association Study Confirms SNPs in SNCA and the MAPT Region as Common Risk Factors for Parkinson DiseaseANNALS OF HUMAN GENETICS, Issue 2 2010Todd L. Edwards Summary Parkinson disease (PD) is a chronic neurodegenerative disorder with a cumulative prevalence of greater than one per thousand. To date three independent genome-wide association studies (GWAS) have investigated the genetic susceptibility to PD. These studies implicated several genes as PD risk loci with strong, but not genome-wide significant, associations. In this study, we combined data from two previously published GWAS of Caucasian subjects with our GWAS of 604 cases and 619 controls for a joint analysis with a combined sample size of 1752 cases and 1745 controls. SNPs in SNCA (rs2736990, p-value = 6.7 × 10,8; genome-wide adjusted p = 0.0109, odds ratio (OR) = 1.29 [95% CI: 1.17,1.42] G vs. A allele, population attributable risk percent (PAR%) = 12%) and the MAPT region (rs11012, p-value = 5.6 × 10,8; genome-wide adjusted p = 0.0079, OR = 0.70 [95% CI: 0.62,0.79] T vs. C allele, PAR%= 8%) were genome-wide significant. No other SNPs were genome-wide significant in this analysis. This study confirms that SNCA and the MAPT region are major genes whose common variants are influencing risk of PD. [source] Epistatic Interactions between Genomic Regions Containing the COL1A1 Gene and Genes Regulating Osteoclast Differentiation may Influence Femoral Neck Bone Mineral DensityANNALS OF HUMAN GENETICS, Issue 2 2007Tie-Lin Yang Summary Bone mineral density (BMD) is a primary risk indicator of osteoporotic fractures, which are largely determined by the actions of multiple genes. Genetic linkage studies have seldom explored epistatic interaction of genes for BMD. To evaluate potential genetic interactions for BMD at the femoral neck (FN) we conducted a variance component linkage analysis, to test epistatic effects between the genomic region containing the COL1A1 (collagen type I alpha 1) gene and the genomic regions containing genes regulating osteoclast differentiation (e.g. TNFRSF11A encoding RANK (receptor for activation of nuclear factor kappa B), TNFSF11 encoding RANKL (RANK ligand), IL1A (interleukin-1 alpha), IL6 (interleukin-6), etc) in 3998 Caucasian subjects from 434 pedigrees. We detected significant epistatic interactions between the regions containing COL1A1 with IL6 (p = 0.004) and TNFRSF1B encoding TNFR2 (tumor necrosis factor receptor 2) (p = 0.003), respectively. In summary, we identified the epistatic effects on BMD between regions containing several prominent candidate genes. Our results suggested that the IL6 and TNFRSF1B genes may regulate FN BMD variation through interactions with the COL1A1 gene, which should be substantiated by other, or population-based, association studies. [source] Role of the urate transporter SLC2A9 gene in susceptibility to gout in New Zealand M,ori, Pacific Island, and Caucasian case,control sample setsARTHRITIS & RHEUMATISM, Issue 11 2009Jade E. Hollis-Moffatt Objective To examine the role of genetic variation in the renal urate transporter SLC2A9 in gout in New Zealand sample sets of M,ori, Pacific Island, and Caucasian ancestry and to determine if the M,ori and Pacific Island samples could be useful for fine-mapping. Methods Patients (n= 56 M,ori, 69 Pacific Island, and 131 Caucasian) were recruited from rheumatology outpatient clinics and satisfied the American College of Rheumatology criteria for gout. The control samples comprised 125 M,ori subjects, 41 Pacific Island subjects, and 568 Caucasian subjects without arthritis. SLC2A9 single-nucleotide polymorphisms rs16890979 (V253I), rs5028843, rs11942223, and rs12510549 were genotyped (possible etiologic variants in Caucasians). Results Association of the major allele of rs16890979, rs11942223, and rs5028843 with gout was observed in all sample sets (P = 3.7 × 10,7, 1.6 × 10,6, and 7.6 × 10,5 for rs11942223 in the M,ori, Pacific Island, and Caucasian samples, respectively). One 4-marker haplotype (1/1/2/1; more prevalent in the M,ori and Pacific Island control samples) was not observed in a single gout case. Conclusion Our data confirm a role of SLC2A9 in gout susceptibility in a New Zealand Caucasian sample set, with the effect on risk (odds ratio >2.0) greater than previous estimates. We also demonstrate association of SLC2A9 with gout in samples of M,ori and Pacific Island ancestry and a consistent pattern of haplotype association. The presence of both alleles of rs16890979 on susceptibility and protective haplotypes in the M,ori and Pacific Island sample is evidence against a role for this nonsynonymous variant as the sole etiologic agent. More extensive linkage disequilibrium in M,ori and Pacific Island samples suggests that Caucasian samples may be more useful for fine-mapping. [source] Pharmacokinetics of sabeluzole and dextromethorphan oxidation capacity in patients with severe hepatic dysfunction and healthy volunteersBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2001G. P. Pageaux Aims, The primary objective of this study was to determine how the pharmacokinetics of sabeluzole, an investigational drug with specific effects on memory and learning abilities, are affected by chronic liver disease. Since sabeluzole is metabolised by CYP2D6, a secondary objective was to study the correlation between CYP2D6 activity (as assessed by the dextromethorphan dextrorphan metabolic ratio) and hepatic dysfunction. Methods, The single-dose pharmacokinetics of sabeluzole (10 mg) was compared in 10 healthy Caucasian subjects and 10 patients with severe hepatic dysfunction. The urinary dextromethorphan/dextrorphan (DMP/DRP) metabolic ratio was determined after intake of 20 mg dextromethorphan (NODEX® capsules). Results, The terminal half-life of sabeluzole was significantly prolonged in subjects with severe hepatic dysfunction vs healthy subjects (respectively 39.3 ± 11.5 h; 17.5 ± 10.2 h (mean ±,s.d.)). The areas under the curve (AUC) were significantly higher in subjects with severe hepatic dysfunction than in healthy volunteers (681 ± 200 ng ml ,1h vs 331 ± 282 ng ml ,1h). There was a significant correlation between the AUC(0,,) and the DMP/DRP metabolic ratio in healthy volunteers and subjects with severe hepatic dysfunction. AUC was greater and elimination of sabeluzole slower in poor metabolizers compared with extensive metabolizers. Conclusions, These results suggest that a) sabeluzole dose should be reduced in patients with severe hepatic dysfunction and b) the AUC of sabeluzole is linked to individual CYP2D6 activity. [source] Homozygosis for (12) CA repeats in the first intron of the human IFN- , gene is significantly associated with the risk of aplastic anaemia in Caucasian populationBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2004Carlo Dufour Summary Interferon- , (IFN- ,) mediates the final damage of the stem cell compartment in Aplastic Anaemia (AA). Normal subjects homozygous for 12 (CA) repeats of polymorphism variable number of dinucleotide (CA) repeat (VNDR) in position 1349 of the IFN- , gene (IFNG) were shown to overproduce IFN- ,in vitro. We studied the distribution of polymorphism VNDR 1349 of IFNG in 67 Caucasian AA patients and in normal controls. Genotype (CA)12-12, (homozygosis for allele 2) and the single allele 12 were significantly more frequent (P = 0·005 and 0·004 respectively) in patients versus controls. The polymorphism was equally distributed in AA patients regardless of their response to immunosuppression. Homozygosity for 12 (CA) repeats of polymorphism VNDR 1349 of IFNG is strongly associated with the risk of AA in Caucasian subjects. [source] Adiponectin levels are high in children with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiencyACTA PAEDIATRICA, Issue 5 2009Thomas MK Völkl Abstract Objective: It has been shown that adiponectin serves as an insulin-sensitizing adipokine. Serum concentrations of adiponectin are low in children with obesity, and increase with fat mass loss, indicating that adiponectin can serve as a biomarker. Since the prevalence of overweight and obesity is increased in children with congenital adrenal hyperplasia (CAH), our study aimed to evaluate serum levels of adiponectin in a cohort of CAH children and adolescents, and their associations with clinical parameters such as chronological age (CA), body mass index (BMI), Tanner stage (TS), medication and metabolic control. Patients and methods: We studied 51 patients, aged between 5.6 and 19.6 years (median 11.8; 30 females, 21 males), cross-sectionally. All patients had genetically confirmed CAH and received standard steroid substitution therapy. Adiponectin was measured by an enzyme linked immunoassay. Since BMI SDS of the CAH cohort were significantly higher compared to the reference population, we built matched pairs with healthy Caucasian subjects from a normal representative cohort for sex, Tanner stage, chronologic age and BMI. Results: Adiponectin concentrations were significantly higher in CAH patients (median 11 ,g/L) compared to the matched controls (6.7 ,g/L, p < 0.0001). Correlation analyses in CAH patients revealed a significant inverse relationship between adiponectin and CA, TS, BMI, serum DHEAS and serum testosterone, but no correlation with hydrocortisone and fludrocortisone dosage. Conclusion: Currently, the importance of the elevated adiponectin concentrations in CAH children for risk assessment is not clear. However, our data imply that besides adequate metabolic control of glucocorticoid substitution, a long-term follow-up of other metabolic markers of insulin resistance should be conducted in CAH patients. [source] Telomere length and obesityACTA PAEDIATRICA, Issue 7 2008Raffaella Zannolli Abstract Aim: To assess the telomere length in apparently healthy obese and normal-weight subjects. Methods: Seventy-six Caucasian subjects were chosen including 53 children (age 8.2 ± 3.5 years) and 23 adults (age 40.5 ± 8.4 years). Among these, 22 (12 children and 10 adults) were obese with a body mass index (BMI, kg/m2) > 2 SD above the norm. Bioelectrical impedance analysis (BIA), measured with a multiple frequency analyzer, was used to estimate body composition. DNA extraction from white blood cells was used to estimate the telomere length by detection of terminal restriction fragments (TRF). Results: No difference was found between the TRF lengths of obese and normal children. Obese adults had shorter TRF lengths than adults who were not obese (mean TRF length difference, ,884.5; 95% confidence intervals ,1727 to ,41.8; t= 2.183; df = 17; p < 0.041). Conclusions: Obese adults have shorter telomeres than their normal-weight counterparts, while this phenomenon is not present in childhood. [source] Liver dysfunction in paediatric obesity: a randomized, controlled trial of metforminACTA PAEDIATRICA, Issue 9 2007Michael Freemark Abstract Aim: In a previous study we showed that metformin reduced BMI z -scores and fasting glucose and insulin concentrations, and increased whole body insulin sensitivity in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. We analyzed the data from this study to determine (a) if metformin reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations during the 6-month trial, and (b) if the response to pharmacotherapy varied along gender or ethnic lines. Methods: The 6-month trial was randomized, double blinded and placebo controlled; a total of 14 metformin-treated (500 mg bid) and 15 placebo-treated subjects completed the study. There were no dietary restrictions. Results: In obese adolescents fed ad libitum, metformin (a) prevented the rise in ALT concentrations that were observed in placebo-treated subjects at the 3 to 5 month time-points (p < 0.05); (b) reduced (p < 0.01) the percentage of all ALT values exceeding 40 U/L; and (c) caused a modest (10%) but statistically significant (p < 0.05) reduction in serum ALT in Caucasian subjects. Metformin had no effect on ALT levels or the ALT to AST ratio in the five African American adolescents enrolled in the study but reduced their fasting insulin concentrations from 26.1 to 19.5 ,U/mL (p < 0.05). Conclusions: Our findings suggest that metformin might reduce the rates or severity of liver dysfunction in selected high-risk adolescents. [source] Single nucleotide polymorphism in CTH associated with variation in plasma homocysteine concentrationCLINICAL GENETICS, Issue 6 2004J Wang Plasma total homocysteine (tHcy) concentration, an independent risk factor of atherosclerosis, has numerous genetic and environmental determinants. While the thermolabile polymorphism in MTHFR encoding methylenetetrahydrofolate reductase is the best-studied genetic factor associated with variation in plasma tHCy, other candidate genes are being evaluated. Recently, we discovered that cystathioninuria was caused by mutations in the CTH gene encoding cystathionine ,-lyase, an enzyme that converts cystathionine to cysteine in the trans-sulfuration pathway. We also identified a common single nucleotide polymorphism (SNP), namely c.1364G>T (S403I) in exon 12 of CTH. In the current analysis, we studied the association of genotypes of this SNP with plasma tHcy concentrations in 496 Caucasian subjects. CTH 1364T/T homozygotes had significantly higher mean plasma tHcy concentration than subjects with other genotypes, and the effect sizes of CTH and MTHFR genotypes were similar. The findings suggest that common variation in CTH may be a determinant of plasma tHcy concentrations. [source] | |||||||||||||