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 < or = 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.
Steno Diabetes Center, Niels Steensens Vej 2, DK-2820, Gentofte, Denmark. skto@steno.dk
Signe S
SS
Torekov
Lesli H
LH
Larsen
Charlotte
C
Glümer
Knut
K
Borch-Johnsen
Torben
T
Jørgensen
Jens J
JJ
Holst
Ole D
OD
Madsen
Torben
T
Hansen
Oluf
O
Pedersen
D001120:Arginine / Q000235:genetics*; D015992:Body Mass Index; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics*; D016017:Odds Ratio; D010375:Pedigree; D019894:Peptide YY / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D017384:Sequence Deletion
D019894:Peptide YY; D004247:DNA; D001120:Arginine