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Caucasian Cohort (caucasian + cohort)
Selected AbstractsAssociation of DLG5 variants with inflammatory bowel disease in the New Zealand caucasian population and meta-analysis of the DLG5 R30Q variant,INFLAMMATORY BOWEL DISEASES, Issue 9 2007Brian L. Browning PhD Abstract Background: Variants in the DLG5 gene have been associated with inflammatory bowel disease (IBD) in samples from some, but not all populations. In particular, 2 nonsynonymous single-nucleotide polymorphisms (SNPs), R30Q (rs1248696) and P1371Q (rs2289310), have been associated with an increased risk of IBD, and a common haplotype (called haplotype "A") has been associated with reduced risk. Methods: We genotyped R30Q, P1371Q, and a haplotype A tagging SNP (rs2289311) in a New Zealand Caucasian cohort of 389 Crohn's disease (CD) patients, 406 ulcerative colitis (UC) patients, and 416 population controls. Each SNP was tested for association with disease susceptibility and clinical phenotypes. We also performed a meta-analysis of R30Q data from published association studies. Results: The haplotype A tagging SNP was associated with reduced risk of IBD at the 0.05 significance level (P = 0.036) with an allelic odds ratio of 0.83 (95% confidence interval [CI]: 0.69,0.99). Association with haplotype A was strongest (odds ratio ,0.57) in UC patients with familial IBD or extraintestinal manifestations. The R30Q and P1371Q polymorphisms were not significantly associated with UC, CD, or IBD. Analysis of male and female data did not find any gender-specific associations. Meta-analysis gave no evidence of association of R30Q with IBD. Conclusions: Meta-analysis demonstrates that the minor allele of R30Q is not a risk factor for IBD across populations. This study provides some evidence that DLG5 haplotype A is associated with reduced risk of IBD in the New Zealand Caucasian population, but this association will need to be replicated in an independent sample. (Inflamm Bowel Dis 2007) [source] Prevalence of metabolic markers of insulin resistance in offspring of gestational diabetes pregnanciesPEDIATRIC DIABETES, Issue 1 2008Erin J Keely In utero hyperglycemia has been associated with insulin resistance (IR) in children; however, there are limited data in low-risk populations. The purpose of this study was to describe the prevalence of metabolic markers of IR in a primarily Caucasian cohort of gestational diabetes mellitus (GDM) offspring aged 7,11 yr (mean 9.1) and to correlate offspring with maternal indexes. Sixty-eight children were recruited through a follow-up study of women who participated in a randomized controlled trial of minimal intervention vs. tight glycemic control for GDM. All participants had a fasting plasma glucose (FPG), insulin, total cholesterol, high-density lipoprotein cholesterol (HDL-chol), triglyceride (TG) level, and a 2-h oral glucose tolerance test. We calculated homeostasis model assessment (HOMA) and recorded body mass index and waist circumference (WC). Criteria for metabolic syndrome for children included: FPG > 6.0 mmol/L, HDL-chol < 1.03 mmol/L, TG > 1.24 mmol/L, WC > 90% for age and gender, and 2-h glucose > 7.8 mmol/L. Among these children, 45 (66%), 17 (25%), 5 (7%), and 1 (1.5%) had zero, one, two, or three metabolic markers of IR, respectively. Hypertriglyceridemia (21%) was most prevalent, with no child having an elevated FPG. WC (p = 0.018) and TG (p = 0.005) were strong predictors of IR in the offspring after adjustment for age, gender, birthweight, family history, and maternal IR. Maternal and offspring HDL-chol, TG, WC, and HOMA but not fasting or 2-h glucose levels were significantly correlated. We conclude that metabolic markers of IR in children exposed to GDM may be present in the absence of abnormal fasting or 2-h glucose values. Screening strategies that focus on glucose levels may need to be reconsidered to institute early intervention with lifestyle changes for children at risk. [source] The shared epitope hypothesis in rheumatoid arthritis: Evaluation of alternative classification criteria in a large UK Caucasian cohortARTHRITIS & RHEUMATISM, Issue 5 2008Ann W. Morgan Objective Many classification systems for the HLA,DRB1 allelic association with rheumatoid arthritis (RA) have been reported, but few have been validated in additional populations. We sought to evaluate 3 different DRB1 allele classification systems in a large cohort of Caucasian RA patients and control subjects in the UK. Methods HLA,DRB1 typing was undertaken in 1,325 Caucasian RA patients and 462 healthy Caucasian controls who were residents of the UK. Logistic regression analyses were performed to investigate the different classification systems. Results We confirmed the association between the susceptibility alleles S2 and S3P, as proposed by Tezenas du Montcel, and the presence of RA in UK Caucasians. A significant hierarchy of risk was observed within the S3P allele group. There was no evidence of a significant association between DRB1*1001 and RA. Our data did not support the hypothesis that an isoleucine at position 67 conferred protection against RA, other than in contrast to the susceptibility alleles. However, the presence of an aspartic acid at amino acid 70 did appear to confer some degree of protection. Conclusion We were unable to fully substantiate any of the 3 recent revisions of the shared epitope hypothesis in this large cohort of Caucasian RA patients and control subjects in the UK. This reinforces the importance of evaluating disease susceptibility alleles in different Caucasian populations as well as in other ethnic groups. In particular, it will be important to clarify the precise DRB1 association in a given population before DRB1 genotyping is incorporated into clinical diagnostic or treatment algorithms. [source] Rheumatoid arthritis association with the FCRL3 ,169C polymorphism is restricted to PTPN22 1858T,homozygous individuals in a Canadian populationARTHRITIS & RHEUMATISM, Issue 12 2006William G. Newman Objective Variants in genes encoding the Fc receptor,like 3 (FcRL-3) and the class II major histocompatibility complex (MHC) transactivator proteins have been associated with an increased risk of rheumatoid arthritis (RA) in Japanese and Nordic populations, respectively. The aim of this study was to investigate these associations in a Canadian Caucasian cohort of RA cases and healthy controls. Methods A total of 1,187 RA patients and 462 healthy controls were genotyped for FCRL3 and MHC2TA gene variants associated with RA. Epistasis between the FCRL3 ,169C and the PTPN22 1858T variants was also examined. Results An association was detected between RA and both the FCRL3 ,169C allele (OR 1.19, P = 0.023) and the homozygous genotype (OR 1.41, P = 0.027), but association of the MHC2TA promoter region variant (,168G) with RA was not replicated. Stratification of the RA cohort by PTPN22 genotypes revealed the FCRL3 risk variant and RA association was stronger in the patient subgroup lacking PTPN22 1858T variants (P = 0.004) and was not detectable in the subgroup with PTPN22 1858T variants (P = 0.52). The PTPN22 association with RA was greater in the absence than in the presence of the FCRL3 ,169C allele (P = 0.0008 versus P = 0.001). The PTPN22 1858T variant also increased the risk of autoimmune thyroid disease (AITD) in the RA patients, whereas the FCRL3 risk variant was protective against AITD. Conclusion Our findings support an association of RA with an FCRL3 functional polymorphism and reveal that this association is stronger in the absence of PTPN22 risk genotypes. These findings support a genetic heterogeneity across RA populations, suggesting that both the FCRL3 and PTPN22 genes play roles in RA susceptibility, but in different individuals. [source] Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevityAGING CELL, Issue 4 2009Ludmila Pawlikowska Summary The insulin/IGF1 signaling pathways affect lifespan in several model organisms, including worms, flies and mice. To investigate whether common genetic variation in this pathway influences lifespan in humans, we genotyped 291 common variants in 30 genes encoding proteins in the insulin/IGF1 signaling pathway in a cohort of elderly Caucasian women selected from the Study of Osteoporotic Fractures (SOF). The cohort included 293 long-lived cases (lifespan , 92 years (y), mean ± standard deviation (SD) = 95.3 ± 2.2y) and 603 average-lifespan controls (lifespan , 79y, mean = 75.7 ± 2.6y). Variants were selected for genotyping using a haplotype-tagging approach. We found a modest excess of variants nominally associated with longevity. Nominally significant variants were then replicated in two additional Caucasian cohorts including both males and females: the Cardiovascular Health Study and Ashkenazi Jewish Centenarians. An intronic single nucleotide polymorphism in AKT1, rs3803304, was significantly associated with lifespan in a meta-analysis across the three cohorts (OR = 0.78 95%CI = 0.68,0.89, adjusted P = 0.043); two intronic single nucleotide polymorphisms in FOXO3A demonstrated a significant lifespan association among women only (rs1935949, OR = 1.35, 95%CI = 1.15,1.57, adjusted P = 0.0093). These results demonstrate that common variants in several genes in the insulin/IGF1 pathway are associated with human lifespan. [source] | ||||||||||