title: Analysis of separate and combined effects of common variation in KCNJ11 and PPARG on risk of type 2 diabetes.
abstract: The separate and combined effects of the PPARG Pro(12)Ala polymorphism and the KCNJ11 Glu(23)Lys polymorphisms on risk of type 2 diabetes were investigated in relatively large-scale, case-control studies. Separate effects of the variants were examined among 1187/1461 type 2 diabetic patients and 4791/4986 middle-aged, glucose-tolerant subjects. The combined analysis involved 1164 type 2 diabetic patients and 4733 middle-aged, glucose-tolerant subjects. In the separate analyses, the K allele of the KCNJ11 Glu(23)Lys associated with type 2 diabetes (odds ratio, 1.19; P = 0.0002), whereas the PPARG Pro(12)Ala showed no significant association with type 2 diabetes. The combined analysis indicated that the two polymorphisms acted in an additive manner to increase the risk of type 2 diabetes, and we found no evidence for a synergistic interaction between them. Analysis of a model with equal additive effects of the two variants showed that the odds ratio for type 2 diabetes increased with 1.14/risk allele (P = 0.003). Together, the two polymorphisms conferred a population-attributable risk for type 2 diabetes of 28%. In conclusion, our results showed no evidence of a synergistic interaction between the KCNJ11 Glu(23)Lys and PPARG Pro(12)Ala polymorphisms, but indicated that they may act in an additive manner to increase the risk of type 2 diabetes.
authors.affiliation: Steno Diabetes Center and Hagedorn Research Institute, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark.
authors.forename: Sara K
authors.initials: SK
authors.lastname: Hansen
authors.forename: Eva-Maria D
authors.initials: EM
authors.lastname: Nielsen
authors.forename: Jakob
authors.initials: J
authors.lastname: Ek
authors.forename: Gitte
authors.initials: G
authors.lastname: Andersen
authors.forename: Charlotte
authors.initials: C
authors.lastname: Glümer
authors.forename: Bendix
authors.initials: B
authors.lastname: Carstensen
authors.forename: Peter
authors.initials: P
authors.lastname: Mouritzen
authors.forename: Thomas
authors.initials: T
authors.lastname: Drivsholm
authors.forename: Knut
authors.initials: K
authors.lastname: Borch-Johnsen
authors.forename: Torben
authors.initials: T
authors.lastname: Jørgensen
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
mesh_terms: D000328:Adult; D000409:Alanine; D019943:Amino Acid Substitution; D015992:Body Mass Index; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005973:Glutamine; D006801:Humans; D008239:Lysine; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D047495:PPAR gamma / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011392:Proline; D012307:Risk Factors; D000099161:Kcnj11 Channel
chemical_list: D000409:Alanine; D005973:Glutamine; D008239:Lysine; D047495:PPAR gamma; D024661:Potassium Channels, Inwardly Rectifying; D011392:Proline; D000099161:Kcnj11 Channel