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Variants of the Transcription Factor 7-Like 2 (TCF7L2) Gene are Associated with Type 2 Diabetes in an African American Population Enriched for Nephropathy

¹Center for Human Genomics,
²Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC;
³Center for Public Health Genomics,
⁴Department of Medicine,
⁵Department of Biochemistry and Molecular Genetics,
⁶Department of Public Health Sciences, University of Virginia, Charlottesville, VA;
⁷Division of Public Health Sciences,
⁸Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC.

Correspondence: msale{at}virginia.edu

Key Words: African American • association • type 2 diabetes • haplotype

Objective:Recently, variants in the TCF7L2 gene have been reported to be associated with type 2 diabetes (T2DM) across multiple Europid populations, but only one small sample of African American (AA) T2DM patients has been examined. Our objective was to investigate the importance of TCF7L2 in a larger AA case-control population.

Research Design and Methods:We investigated SNPs in 6 known T2DM genes in 577 AA cases with T2DM enriched for nephropathy and 596 AA controls. Additionally, we genotyped 70 ancestry-informative markers (AIMs) to apply adjustments for differences in ancestral proportions.

Results:The most significant associations were observed with TCF7L2 intron 3 SNPs rs7903146 (additive P=4.10x10^-6, OR 1.51; admixture-adjusted P_a=3.77x10^-6) and rs7901695 (P=0.001, OR 1.30; P_a=0.003). The 2-SNP haplotype containing these SNPs was also associated with T2DM (P=3x10^-5). Modest associations were also seen with TCF7L2 intron 4 SNPs rs7895340, rs11196205 and rs12255372 (0.01<P<0.05; 0.03<P_a<0.08), and KCNJ11 and HNF4A SNPs (0.01<P<0.05; 0.01<P_a<0.41). No significant associations were detected with genotyped CAPN10, PPARG, and TCF1 SNPs.

Conclusions:This study indicates that variants in the TCF7L2 gene significantly contribute to diabetes susceptibility in AA populations.

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