Studies of the Pro12Ala polymorphism of the PPAR-γ gene in the Danish MONICA cohort:: Homozygosity of the Ala allele confers a decreased risk of the insulin resistance syndrome

被引:110
作者
Frederiksen, L
Brodbæk, K
Fenger, M
Jorgensen, T
Borch-Johnsen, K
Madsbad, S
Urhammer, SA
机构
[1] Univ Copenhagen, Hvidovre Hosp, Dept Endocrinol, DK-2650 Hvidovre, Denmark
[2] Univ Copenhagen, Hvidovre Hosp, Dept Clin Biochem, DK-2650 Hvidovre, Denmark
[3] Glostrup Univ Hosp, Ctr Prevent Med, DK-2600 Glostrup, Denmark
[4] Steno Diabet Ctr, DK-2820 Gentofte, Denmark
关键词
D O I
10.1210/jc.87.8.3989
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The Pro12Ala polymorphism of PPAR-gamma2 has been shown to influence insulin sensitivity and the risk of type 2 diabetes in various ethnic populations. We examined whether the polymorphism was related to the insulin resistance syndrome (IRS) among nondiabetic Danish subjects. The Pro12Ala variant was examined using PCR-restriction fragment length polymorphism in a phenotypically well characterized population-based sample of 2245 nondiabetic subjects. The study participants were characterized by a number of anthropometric and biochemical measurements and the European Group for the Study of Insulin Resistance criteria enabling a classification of the study population in an IRS group and a non-IRS group. The allelic frequency of the Pro12Ala polymorphism in the total study sample was 14% (95% confidence interval, 13-15%). Two hundred ninety-four subjects fulfilled the European Group for the Study of Insulin Resistance criteria defining the IRS. The frequency of the Ala allele was 12.6% in the IRS group and 14.2% among subjects classified as not having the IRS (P = 0.15). However, the frequency of the variant in the homozygous form was significantly lower in the IRS group [0.7% (0-1.6%)] compared with the frequency in the non-IRS group [2.8% (2.1-3.5%); P = 0.02; odds ratio, 0.24 (0.06-0.99)]. Moreover, in the total study population, homozygous carriers of the variant had lower levels of fasting serum triglyceride [1.1 +/- 0.4 mmol/liter (means SD) VS. 1.4 +/- 0.9 mmol/liter; P = 0.04] and a lower diastolic blood pressure (79 +/- 8 mm Hg vs. 82 +/- 11 min Hg; P = 0.01) compared with wild-type carriers. The same tendency was observed with regard to the homeostasis model assessment estimate of insulin resistance (P = 0.16). There were no differences between genotype groups with respect to measures of body composition (BMI and waist circumference). In conclusion, homozygosity of the codon 12 variant of PPAR-gamma2 confers a reduced risk of the IRS among Danish Caucasian subjects.
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页码:3989 / 3992
页数:4
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