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).