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

被引：47

作者：

Hansen, SK

Nielsen, EMD

Ek, J

Andersen, G

Glümer, C

Carstensen, B

Mouritzen, P

Drivsholm, T

Borch-Johnsen, K

Jorgensen, T

Hansen, T

Pedersen, O

机构：

[1] Steno Diabet Ctr, DK-2820 Gentofte, Denmark

[2] Hagedorn Res Inst, DK-2820 Gentofte, Denmark

[3] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark

[4] Exiqon AS, Vedbaek, Denmark

[5] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark

来源：

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2005年 / 90卷 / 06期

关键词：

D O I：

10.1210/jc.2004-1942

中图分类号：

R5 [内科学];

学科分类号：

1002 [临床医学]; 100201 [内科学];

摘要：

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.

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收藏

页码：3629 / 3637

页数：9

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