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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: African Americans, Case-Control Studies, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Introns, Male, Middle Aged, Polymorphism, Single Nucleotide, Reference Values, TCF Transcription Factors, Transcription Factor 7-Like 2 Protein, United States.
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Are variants of the transcription factor 7-like 2 ( TCF7L2 ) gene associated with type 2 diabetes in an African-American population enriched for nephropathy? Context: Recently, variants in the TCF7L2 gene have been reported to be associated with type 2 diabetes across multiple Europid populations, but only one small sample of African-American type 2 diabetic patients has been examined. Our objective was to investigate the importance of TCF7L2 in a larger African-American case-control population. We investigated single nucleotide polymorphisms (SNPs) in six known type 2 diabetes genes in 577 African-American case subjects with type 2 diabetes enriched for nephropathy and 596 African-American control subjects. Additionally, we genotyped 70 ancestry-informative markers (AIMs) to apply adjustments for differences in ancestral proportions. The most significant associations were observed with TCF7L2 intron 3 SNPs rs7903146 (additive P = 4.10 x 10(-6), odds ratio [OR] 1.51; admixture-adjusted P(a) = 3.77 x 10(-6)) and rs7901695 (P = 0.001, OR 1.30; P(a) = 0.003). The 2-SNP haplotype containing these SNPs was also associated with type 2 diabetes (P = 3 x 10(-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), as well as with ATP-sensitive inwardly rectifying potassium channel subunit Kir6.2 (KCNJ11) and hepatocyte nuclear factor 4-alpha (HNF4A) SNPs (0.01 < P < 0.05; 0.01 < P(a) < 0.41). No significant associations were detected with genotyped calpain 10 (CAPN10), peroxisome proliferator-activated receptor gamma (PPARG), and transcription factor 1 (TCF1) SNPs.
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This study indicates that variants in the TCF7L2 gene significantly contribute to diabetes susceptibility in African-American populations. Final Decision: yes