Association of Pro12Ala Polymorphism in Peroxisome Proliferator–Activated Receptor γ With Pre-Diabetic Phenotypes
Meta-analysis of 57 studies on nondiabetic individuals
- Anke Tönjes, MD1,
- Markus Scholz, PHD2,
- Markus Loeffler, MD2 and
- Michael Stumvoll, MD1
- 1IIIrd Medical Department, University of Leipzig, Leipzig, Germany
- 2Institute of Medical Statistics and Epidemiology University of Leipzig, Leipzig, Germany
- Address correspondence and reprint requests to Michael Stumvoll, MD, University of Leipzig, IIIrd Medical Department, Philipp-Rosenthal-Str. 27, 04103 Leipzig, Germany. E-mail: michael.stumvoll{at}medizin.uni-leipzig.de
Abstract
OBJECTIVE—The provariant of the Pro12Ala polymorphism in peroxisome proliferator–activated receptor (PPAR)γ has been identified as a risk allele for type 2 diabetes. The purpose of the present study was to reveal a significant association with pre-diabetic phenotypes in nondiabetic individuals based on a systematic meta-analysis of all available published evidence.
RESEARCH DESIGN AND METHODS—We performed a classical meta-analysis of data from ∼32,000 nondiabetic subjects in 57 studies to assess the effect of the Pro12Ala polymorphism on pre-diabetic traits.
RESULTS—In the global comparison, there were no differences in BMI, glucose, insulin, or homeostasis model assessment of insulin resistance between the Pro/Pro and X/Ala genotype. However, in the Caucasian subgroup, the X/Ala genotype was associated with significantly increased BMI. In the obese subgroup (BMI >30 kg/m2), fasting glucose (P = 0.041) and insulin resistance (by homeostasis model analysis) (P = 0.020) were significantly greater in the Pro/Pro group. In subjects with the homozygous Ala/Ala genotype, fasting insulin was significantly lower compared with the Pro/Pro genotype (P = 0.040, NAla/Ala = 154).
CONCLUSIONS—Across all studies, the Pro12Ala polymorphism had no significant effect on diabetes-related traits. Only in selected subgroups, such as Caucasians and obese subjects, did we see an association of the Ala allele with greater BMI and greater insulin sensitivity. This demonstrates the importance for appropriate stratification of analyses by environmental or other genetic factors. Meta-analysis of Ala/Ala homozygotes more clearly demonstrated the association with greater insulin sensitivity of carriers of the Ala allele.
- HOMA-IR, homeostasis model assessment of insulin resistance
- OGTT, oral glucose tolerance test
- PPAR, peroxisome proliferator–activated receptor
Footnotes
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A.T. and M.S. contributed equally to this work.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.
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- Accepted August 4, 2006.
- Received March 7, 2006.
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