Tönjes Anke, Scholz Markus, Loeffler Markus, Stumvoll Michael
University of Leipzig, IIIrd Medical Department, Philipp-Rosenthal-Str. 27, 04103 Leipzig, Germany.
Diabetes Care. 2006 Nov;29(11):2489-97. doi: 10.2337/dc06-0513.
The provariant of the Pro12Ala polymorphism in peroxisome proliferator-activated receptor (PPAR)gamma 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.
We performed a classical meta-analysis of data from approximately 32,000 nondiabetic subjects in 57 studies to assess the effect of the Pro12Ala polymorphism on pre-diabetic traits.
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/m(2)), 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, N(Ala/Ala) = 154).
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.
过氧化物酶体增殖物激活受体（PPAR）γ中Pro12Ala多态性的前变体已被确定为2型糖尿病的风险等位基因。本研究的目的是基于对所有已发表的可用证据进行系统的荟萃分析，揭示非糖尿病个体中该多态性与糖尿病前期表型之间的显著关联。
我们对57项研究中约32000名非糖尿病受试者的数据进行了经典荟萃分析，以评估Pro12Ala多态性对糖尿病前期特征的影响。
在总体比较中，Pro/Pro和X/Ala基因型之间在体重指数（BMI）、血糖、胰岛素或胰岛素抵抗的稳态模型评估方面没有差异。然而，在白种人亚组中，X/Ala基因型与BMI显著升高相关。在肥胖亚组（BMI>30kg/m²）中，Pro/Pro组的空腹血糖（P=0.041）和胰岛素抵抗（通过稳态模型分析）（P=0.020）显著更高。在纯合Ala/Ala基因型的受试者中，空腹胰岛素与Pro/Pro基因型相比显著更低（P=0.040，N(Ala/Ala)=154）。
在所有研究中，Pro12Ala多态性对糖尿病相关特征没有显著影响。仅在特定亚组中，如白种人和肥胖受试者，我们才观察到Ala等位基因与更高的BMI和更高的胰岛素敏感性相关。这证明了按环境或其他遗传因素对分析进行适当分层的重要性。对Ala/Ala纯合子的荟萃分析更清楚地证明了Ala等位基因携带者与更高胰岛素敏感性之间的关联。
