rs7903146

This SNP in TCF7L2 influences the risk of Type-2 diabetes (T2D). This SNP is also known as IVS3C>T. rs7903146(C;T) rs7903146(T;T) strongly predicted future type-2 diabetes. Considered in context with rs7903146 rs12255372 rs10885406. Note: this is one of two SNPs within the TCF7L2 gene that have been reported to be associated with type-2 diabetes, the other being rs4506565. They have approximately equal power to estimate risk for type-2 diabetes, and the results from one correlate 92% of the time with the other. Full text of the paper is available from from Plos Medicine. Or from NCBI as . TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. reconfirmed in a diverse population Associated in a study of ~1000 Hispanic-Americans with reduced insulin secretion as measured by acute insulin response and adjusted for the degree of insulin sensitivity (p = 0.032). the CT/TT genotypes strongly predicted future type-2 diabetes. The risk T allele was associated with impaired insulin secretion, incretin effects, and enhanced rate of hepatic glucose production. TCF7L2 expression in human islets was increased 5-fold in T2D, particularly in carriers of the TT genotype. This SNP is one of 4 relatively common SNPs reported to represent risk for type-2 diabetes in the DESIR prospective study of 3,877 Caucasian participants. Under an additive model, the odds ratio for the (T) risk allele is 1.45 (CI: 1.2-1.77, p=0.0002). For the 4 SNPs, each risk allele increased type-2 diabetes risk by 1.34x (p=2x10e-6), with an odds ratio of 2.48 (CI: 1.59-3.86) for carriers of 4 or more compared to those with one or none (risk alleles). Contrary to what's been seen in most populations studied so far, the association between rs7903146 and type-2 diabetes apparently does not hold in Arab populations, based on a case-control study of 522 Saudi patients and 346 controls. A HuGE review and meta-analysis including over 35,000 type-2 diabetes cases and 39,000 controls concluded that the Bayesian odds ratio for rs7903146(T;T) homozygotes and (C;T) heterozygotes versus (C;C) homozygotes was 1.968 (95% credible interval (CrI): 1.790 - 2.157) and 1.406 (95% CrI: 1.341 - 1.476), respectively, and the population attributable risk (PAR) for the (C;T)/(T;T) genotypes of this variant is 16.9% overall. Along with 3 other TCF7L2 SNPs, a multiplicative genetic model was indicated. A study of over 13,000 individuals initially free of cancer and followed over 10+ years found that the rs7903146(T) allele was associated with increased risk of colorectal cancer, with an adjusted odds ratio of 1.25 (CI:0.85-1.83) and 2.15 (CI:1.27-3.64) for the (C;T) and (T;T) genotypes, respectively. Does the association with type 2 diabetes hold for youth as well as for adults? Among African American youth, each copy of a rs7903146(T) allele was associated with a 1.97-fold (CI:1.37 - 2.82) increased odds for type 2 diabetes (p?<?0.0001), yet no significant association was detected in non-Hispanic white youth (adjusted odds ratio 1.14; CI: 0.73 - 1.79).

C;C

Normal insulin secretion in the pancreas. This has been confirmed in most races.

C;T

Higher risk for Type 2 Diabetes and Gestational Diabetes. Reduced insulin secretion in the pancreas. This has been confirmed in most races.

T;T

This genotype doubles the risk of Type-2 diabetes, PMID 17671651 and also Gestational Diabetes. Also increased risk of colo-rectal cancer. Reduced insulin secretion in the pancreas. This has been confirmed in most races. In African Americans it even affects young people.