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Analysis of separate and combined effects of common variation in KCNJ11 and PPARG on risk of type 2 diabetes

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Sara Krogh Hansen
  • Eva-Maria D Nielsen
  • Jakob Ek
  • Gitte Andersen
  • Charlotte Glümer
  • Bendix Carstensen
  • Peter Mouritzen
  • Drivsholm, Thomas
  • Knut Borch-Johnsen
  • Torben Jørgensen
  • Torben Hansen
  • Oluf Pedersen
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.
OriginalsprogEngelsk
TidsskriftJournal of Clinical Endocrinology and Metabolism
Vol/bind90
Udgave nummer6
Sider (fra-til)3629-37
Antal sider9
ISSN0021-972X
DOI
StatusUdgivet - 1 jun. 2005

ID: 33030287