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Genetics of Obesity and Diabetes in the IRAS Family Study

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abstract
The prevalence of diabetes and obesity in the United States and abroad makes these common diseases a leading health concern. Research involving the discovery of genes contributing to these diseases is great public health importance. Identification of a gene and/or genes that contribute to the phenotypic variance of obesity and/or glucose homeostasis traits measured in this study could lead to better methods of treatment of these disorders. The population that was used in this study was the Insulin Resistance Atherosclerosis (IRAS) Family Study, which is a multi-center, multi-ethnic population study that examines the genetic contributions to insulin resistance and obesity. Linkage and subsequent candidate gene analysis was performed on 699 African-American individuals from 42 families searching for regions linked to insulin resistance and obesity phenotypes. While the region on chromosome 6 continued to show linkage, the region on chromosome 5 decreased slightly. Candidate gene analysis of the regions on chromosomes 5 and 6 was performed in order to further investigate these linkage regions. Two genes, E2F3 and CDKAL1, on chromosome 6 showed significant associations with subcutaneous adipose tissue (SAT). In E2F3, SNPs rs4710930 and rs6939190, were associated with SAT [Genotypic means: 1/1 (18.62(342)), 1/2 (17.01(142)), 2/2 (17.52(17))]; [1/1 (18.69(353)), 1/2 (17.12(149)), 2/2 (18.48(15))] (p-value=0.0005; 0.002). In addition, CDKAL1 SNP rs9350270 was associated with BMI, WHR, SAT, VAT and waist with the most important association being SAT (p-value=0.008) [Genotypic means: 1/1 (17.59(224)), 1/2 (18.75(243)), 2/2 (17.88(47))]. As noted, the genotypic means show an increase in SAT with an increase in copies of the risk allele. The gene from the chromosome 5 candidate gene analyses that had the most evidence of association with insulin sensitivity, the trait of interest, and the other traits measured was GHR. SI was associated with SNPs rs6870962 (p-value=0.009) [Genotypic means: 1/1 (1.57(400)), 1/2 (1.86(81)), 2/2 (1.94(10))], and rs6883523 (p-value=0.009) [Genotypic means: 1/1 (1.68(371)), 1/2 (1.49(114)), 2/2 (0.82(9))]. In summary, regions that were linked to obesity and glucose homeostasis traits were evaluated for linkage and association. Genes identified within these regions showed various levels of evidence for association with the traits of interest and are candidates for further study.
subject
Obesity
Diabetes
contributor
Proctor, Alexandria (author)
Langefeld, Carl (committee chair)
Lively, Mark (committee member)
Xue, Bingzhong (committee member)
Antinozzi, Peter (committee member)
date
2009-10-21T18:28:32Z (accessioned)
2010-06-18T18:58:12Z (accessioned)
2009-10-21T18:28:32Z (available)
2010-06-18T18:58:12Z (available)
2009-10-21T18:28:32Z (issued)
degree
Biochemistry & Molecular Biology (discipline)
identifier
http://hdl.handle.net/10339/14741 (uri)
language
en_US (iso)
publisher
Wake Forest University
rights
Release the entire work immediately for access worldwide. (accessRights)
title
Genetics of Obesity and Diabetes in the IRAS Family Study
type
Dissertation

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