Laboratory of Molecular Biology, Department of Genetics and Molecular Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
Circ J. 2009 Nov;73(11):2118-24. doi: 10.1253/circj.cj-09-0320. Epub 2009 Sep 10.
The Pro12Ala polymorphism (rs1801282), a nonsynonymous substitution of peroxisome proliferator-activated receptor-gamma (PPARG), has been robustly associated with type 2 diabetes. However, its role in metabolic syndrome (MetS) remains poorly understood. The associations among rs1801282, MetS and surrogate measures of insulin resistance (IR) were investigated in the present study.
A cross-sectional population-based survey of 572 unrelated healthy male Argentinian blood donors with normal findings on medical examination and not taking any medication was conducted. MetS was assessed using the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) criteria, and the HOMA-IR, and QUICKI were calculated. Genotyping of rs1801282 was performed using RFLP-PCR. The prevalence of MetS was 26.2%. The Pro/Ala genotype (and the Ala12 allele) was associated with a high risk for MetS (odds ratio (OR) 1.67 [95% confidence interval (CI) 1.03-2.72], P=0.0394). This was highlighted among nonsmokers (OR 2.20 [95%CI 1.25-3.88], P=0.0059). ANCOVA confirmed an interaction between smoking status and this association (P=0.031). Ala12 carriers had a higher waist circumference than noncarriers (P=0.0065). Among nonsmokers, surrogates of IR, such as HOMA-IR, were significantly higher in Ala12 carriers than in noncarriers (P<0.05).
Healthy men, in particular nonsmokers, carrying the Ala12 allele of PPARG rs1801282 polymorphism, have a high risk for MetS and IR.
过氧化物酶体增殖物激活受体-γ（PPARG）的 Pro12Ala 多态性（rs1801282）是一种非同义替换，与 2 型糖尿病密切相关。然而，其在代谢综合征（MetS）中的作用仍知之甚少。本研究旨在探讨 rs1801282 与 MetS 及胰岛素抵抗（IR）替代指标之间的关系。
对 572 名无关联的健康阿根廷男性献血者进行了横断面人群基础调查，这些献血者体格检查正常，未服用任何药物。采用国家胆固醇教育计划/成人治疗专家组 III（NCEP/ATP III）标准评估 MetS，计算 HOMA-IR 和 QUICKI。采用 RFLP-PCR 检测 rs1801282 的基因型。MetS 的患病率为 26.2%。Pro/Ala 基因型（及 Ala12 等位基因）与 MetS 风险增加相关（比值比[OR]1.67[95%置信区间[CI]1.03-2.72]，P=0.0394）。这种相关性在不吸烟者中更为明显（OR 2.20[95%CI 1.25-3.88]，P=0.0059）。ANCOVA 证实了这种关联与吸烟状态之间存在交互作用（P=0.031）。Ala12 携带者的腰围大于非携带者（P=0.0065）。在不吸烟者中，Ala12 携带者的 IR 替代指标（如 HOMA-IR）显著高于非携带者（P<0.05）。
携带 PPARG rs1801282 多态性 Ala12 等位基因的健康男性，特别是不吸烟者，患 MetS 和 IR 的风险较高。
