This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hansen, S. K. Articles by Pedersen, O. Search for Related Content PubMed PubMed Citation Articles by Hansen, S. K. Articles by Pedersen, O. Related Collections Diabetes and Insulin

Analysis of Separate and Combined Effects of Common Variation in KCNJ11 and PPARG on Risk of Type 2 Diabetes

Steno Diabetes Center and Hagedorn Research Institute (S.K.H., E.-M.D.N., J.E., G.A., C.G., B.C., K.B.-J., T.H., O.P.), Gentofte, Copenhagen, Denmark; Research Center for Prevention and Health, Copenhagen County, Glostrup University Hospital (C.G., T.D., K.B.-J., T.J.), Glostrup, Denmark; Exiqon A/S (P.M.), Vedbæk, Denmark; and Faculty of Health Science, University of Aarhus (K.B.-J., O.P.), Aarhus, Denmark

Address all correspondence and requests for reprints to: Professor Oluf Pedersen, M.D., D.M.Sc., Steno Diabetes Center and Hagedorn Research Institute, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark. E-mail: oluf{at}steno.dk.

The separate and combined effects of the PPARG Pro¹²Ala polymorphism and the KCNJ11 Glu²³Lys 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 Glu²³Lys associated with type 2 diabetes (odds ratio, 1.19; P = 0.0002), whereas the PPARG Pro¹²Ala 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 Glu²³Lys and PPARG Pro¹²Ala polymorphisms, but indicated that they may act in an additive manner to increase the risk of type 2 diabetes.

This article has been cited by other articles:

				H. Staiger, F. Machicao, A. Fritsche, and H.-U. Haring Pathomechanisms of Type 2 Diabetes Genes Endocr. Rev., October 1, 2009; 30(6): 557 - 585. [Abstract] [Full Text] [PDF]

				N. J. Webster, G. J. Searle, P. P. L. Lam, Y.-C. Huang, M. J. Riedel, G. Harb, H. Y. Gaisano, A. Holt, and P. E. Light Elevation in Intracellular Long-Chain Acyl-Coenzyme A Esters Lead to Reduced {beta}-Cell Excitability via Activation of Adenosine 5'-Triphosphate-Sensitive Potassium Channels Endocrinology, July 1, 2008; 149(7): 3679 - 3687. [Abstract] [Full Text] [PDF]

				Y. Yi, L. Dongmei, D. A. Phares, E. P. Weiss, J. Brandauer, and J. M. Hagberg Association between KCNJ11 E23K genotype and cardiovascular and glucose metabolism phenotypes in older men and women Exp Physiol, January 1, 2008; 93(1): 95 - 103. [Abstract] [Full Text] [PDF]

				K. D. Taylor, J. M. Norris, and J. I. Rotter Genome-Wide Association: Which Do You Want First: the Good News, the Bad News, or the Good News? Diabetes, December 1, 2007; 56(12): 2844 - 2848. [Full Text] [PDF]

				Y. Doi, M. Kubo, T. Ninomiya, K. Yonemoto, M. Iwase, H. Arima, J. Hata, Y. Tanizaki, M. Iida, and Y. Kiyohara Impact of Kir6.2 E23K Polymorphism on the Development of Type 2 Diabetes in a General Japanese Population: The Hisayama Study Diabetes, November 1, 2007; 56(11): 2829 - 2833. [Abstract] [Full Text] [PDF]

				L. J. Scott, L. L. Bonnycastle, C. J. Willer, A. G. Sprau, A. U. Jackson, N. Narisu, W. L. Duren, P. S. Chines, H. M. Stringham, M. R. Erdos, et al. Association of Transcription Factor 7-Like 2 (TCF7L2) Variants With Type 2 Diabetes in a Finnish Sample Diabetes, September 1, 2006; 55(9): 2649 - 2653. [Abstract] [Full Text] [PDF]

				G. Sesti, E. Laratta, M. Cardellini, F. Andreozzi, S. Del Guerra, C. Irace, A. Gnasso, M. Grupillo, R. Lauro, M. L. Hribal, et al. The E23K Variant of KCNJ11 Encoding the Pancreatic {beta}-Cell Adenosine 5'-Triphosphate-Sensitive Potassium Channel Subunit Kir6.2 Is Associated with an Increased Risk of Secondary Failure to Sulfonylurea in Patients with Type 2 Diabetes J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2334 - 2339. [Abstract] [Full Text] [PDF]