Association of TCF7L2 Allelic Variations with Gastric Function, Satiation, and GLP-1 Levels

Objective: Genetic variation in transcription factor 7-like 2 (TCF7L2), a regulator of proglucagon processing, is reproducibly associated with type 2 diabetes. GLP-1 alters gastric function and increases satiation. Hypothesis: Genetic variation in TCF7L2 is associated with satiation, gastric motor function, and GLP-1 concentrations. Methods: In 62 adults, a single nucleotide polymorphism (SNP) of TCF7L2 (rs7903146) was genotyped and associations with gastric emptying (GE) of solids and liquids, gastric volume (GV), and satiation (maximum tolerated volume and symptoms after nutrient drink test) were explored using a dominant genetic model, with gender and BMI as covariates. In 50 of the participants, we also measured plasma GLP-1 during fasting and after ingestion of a nutrient drink. Results: Presence of the T allele compared to CC genotype in rs7903146 SNP of the TCF7L2 gene was associated with reduced fasting GV (246.3 +/- 11.4 mL for CC group, compared to 215.7 +/- 11.4 mL for CT/TT group, p = 0.05) and accelerated GE t(1/2) of liquids (26.3 +/- 2.0 minutes for CC compared to 17.7 +/- 1.4 for CT/TT, p < 0.005). There was no significant association of rs7903146 SNP with GE of solids, gastric accommodation, satiation, fasting, or postprandial GLP-1. Conclusion: Our data suggest TCF7L2 is associated with altered gastric functions that may predispose to obesity. Clin Trans Sci 2011; Volume 4: 183-187