Brief Genetics Report Evidence of an Association Between the Arg72 Allele of the Peptide YY and Increased Risk of Type 2 Diabetes

We tested the hypothesis that variants in the gene encoding the prepropeptide YY (PYY) associate with type 2 diabetes and/or obesity. Mutation analyses of DNA from 84 patients with obesity and familial type 2 diabetes identified two polymorphisms, IVS3 68C>T and Arg72Thr, and one rare variant, 151C>A of PYY. The common allele of the Arg72Thr variant associated with type 2 diabetes with an allele frequency of the Arg allele of 0.667 (95% CI 0.658–0.677) among 4,639 glucose-tolerant subjects and 0.692 (0.674–0.710) among 1,326 patients with type 2 diabetes (P 0.005, odds ratio 1.19 [95% CI 1.05–1.35]). The same polymorphism associated with overweight (25 < BMI < 30 kg/m) (P 0.018, 1.15 [1.02– 1.28]). In quantitative trait analyses of a population-based sample of 6,022 subjects, the Arg allele was associated with an increased plasma glucose level 2 h after an oral glucose tolerance test (OGTT) (P 0.03), an increased area under the curve for the post-OGTT plasma glucose level (P 0.03), and a lower insulinogenic index (P 0.01). In conclusion, the common Arg allele of the PYY Arg72Thr variant modestly associates with type 2 diabetes and with type 2 diabetes–related quantitative traits. Diabetes 54:2261–2265, 2005