rs12255372 — TCF7L2

Second TCF7L2 diabetes variant - compounds risk with rs7903146

See your personal result for TCF7L2

Upload your DNA data to find out which genotype you carry and what it means for you.

Upload your DNA data

Works with 23andMe, AncestryDNA, and other DNA test exports. Results in under 60 seconds.

Secondary TCF7L2 Variant

This is the second most-studied variant in the TCF7L2 gene, located in intron 4 approximately 50 kb from the primary variant rs7903146. While rs7903146 is the primary diabetes risk variant, rs12255372 provides additional information about your TCF7L2 haplotype. The two variants are in moderate linkage disequilibrium11 Linkage disequilibrium means these variants tend to be inherited together because they sit close on the same chromosome, within a 92-kb LD block, meaning they are often co-inherited but not always.

The Mechanism

Like rs7903146, this variant sits in a non-coding region and is thought to influence TCF7L2 expression levels, though rs7903146 appears to be the stronger functional driver. The T allele at this position is associated with decreased insulin secretion.

The Evidence

The Pounds Lost trial22 Pounds Lost trial
Mattei et al. Am J Clin Nutr, 2012 also examined rs12255372 and found that TT carriers who consumed a lower-fat diet had greater reductions in body adiposity, which could improve glycemic control.

Practical Implications

Having risk alleles at both rs7903146 and rs12255372 compounds your overall TCF7L2-related diabetes risk. The dietary recommendations are the same: moderate fat intake and a Mediterranean-style eating pattern.

Interactions

This variant is in moderate linkage disequilibrium with rs7903146. If you carry risk alleles at both positions, your overall TCF7L2-related risk is higher.

Nutrient Interactions

dietary fat altered_metabolism

Genotype Interpretations

What each possible genotype means for this variant.

GG Normal TCF7L2 Normal

Normal at this position

You don't carry the risk variant at this secondary TCF7L2 position. About 60% of people of European descent share this genotype. Your diabetes risk from this specific variant is not elevated.

GT Mild Risk Carrier Intermediate

One risk allele at secondary TCF7L2 position

You carry one risk allele at this secondary TCF7L2 position. About 34% of Europeans share this genotype. This adds slightly to diabetes risk, especially in combination with the primary rs7903146 variant.

TT Double Risk High Risk

Two risk alleles at secondary position

You have two risk alleles at this position, adding to overall TCF7L2-related diabetes risk. About 6% of Europeans share this genotype. This is especially significant if you also carry the T allele at rs7903146.