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

¹ Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark
² Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
³ Danish Epidemiology Science Centre and Research Unit for Dietary Studies at the Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark
⁴ Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
⁵ Faculty of Health Science, University of Aarhus, Aarhus, Denmark
⁶ Department of Medical Physiology, University of Copenhagen, Denmark

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/m²) (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.

Abbreviations: HPLC, high-performance liquid chromatography; OGTT, oral glucose tolerance test; NPY, neuropeptide Y; PYY, peptide YY; UTR, untranslated region

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