Vaccaro O, Mancini F P, Ruffa G, Sabatino L, Iovine C, Masulli M, Colantuoni V, Riccardi G
Department of Clinical and Experimental Medicine, II Policlinico, Medical School, Federico II University, Via S Pansini 5, 80131 Naples, Italy.
Clin Endocrinol (Oxf). 2002 Oct;57(4):481-6. doi: 10.1046/j.1365-2265.2002.01618.x.
The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR) gamma gene has been associated in some, but not all, studies with lower body mass index (BMI) and improved insulin sensitivity; how an altered transcriptional activity of PPARgamma2 could influence insulin sensitivity is currently unclear. The free fatty acids (FFAs) released from adipose tissue triglycerides via lipolysis are key mediators of impaired insulin sensitivity; however, no study has described the relationship of the Pro12Ala mutation with circulating levels of FFAs under physiological conditions.
To investigate in a population-based sample of Caucasians the relation of the Pro12Ala polymorphism with plasma concentrations of FFAs and other markers of lipid and glucose metabolism described as components of the insulin resistance syndrome.
Four hundred and thirty-eight nondiabetic employees of the Italian Telephone Company, aged 35-65 years, randomly selected from a total population of 3900 participants in a company-sponsored health screening.
The Pro12Ala polymorphism of the PPARgamma was studied together with plasma FFAs, insulin, glucose, triglycerides, high density lipoprotein (HDL) cholesterol, blood pressure and anthropometry. The Homeostatic Model Assessment (HOMA) index was calculated as a measure of insulin resistance.
Carriers and noncarriers of the Pro12Ala polymorphism showed very similar circulating levels of FFA (0.46 +/- 0.2 vs. 0.47 +/- 0.2, NS); plasma glucose, triglycerides, HDL cholesterol and blood pressure were also similar in the two groups with or without the polymorphism. To allow for the possible confounding effect of obesity, a separate analysis was conducted in overweight (BMI > or = 25 kg/m(2)) and normal-weight people (BMI < 25 kg/m(2)). Circulating plasma FFA concentrations, as well as triglycerides, blood pressure and HOMA, were significantly higher in overweight than normal-weight, as expected, but no significant differences were detected between carriers and noncarriers of the Pro12Ala polymorphism within each BMI group (0.49 +/- 0.2 vs. 0.48 +/- 0.2, NS, and 0.44 +/- 0.2 vs. 0.47 +/- 0.2, NS, in overweight and normal-weight, respectively). The Pro12Ala polymorphism was also analysed across increasing quartiles of FFA concentrations and no relationship was observed between the frequency of the polymorphism and FFA values (overall chi2 = 0.48, NS).
This study does not show any relationship between the Pro12Ala polymorphism of the PPARgamma gene and fasting FFAs in the general population. The possibility of a different handling of FFAs under different conditions (i.e. postprandial) cannot be excluded and remains to be explored.
过氧化物酶体增殖物激活受体（PPAR）γ基因的Pro12Ala多态性在一些（但并非全部）研究中与较低的体重指数（BMI）及改善的胰岛素敏感性相关；目前尚不清楚PPARγ2转录活性的改变如何影响胰岛素敏感性。通过脂解作用从脂肪组织甘油三酯释放的游离脂肪酸（FFA）是胰岛素敏感性受损的关键介质；然而，尚无研究描述在生理条件下Pro12Ala突变与循环FFA水平之间的关系。
在以白种人为基础的样本中研究Pro12Ala多态性与FFA血浆浓度以及作为胰岛素抵抗综合征组成部分的其他脂质和葡萄糖代谢标志物之间的关系。
从意大利电话公司3900名参加公司赞助健康筛查的参与者中随机选取438名年龄在35 - 65岁的非糖尿病员工。
研究PPARγ的Pro12Ala多态性，同时检测血浆FFA、胰岛素、葡萄糖、甘油三酯、高密度脂蛋白（HDL）胆固醇、血压及人体测量学指标。计算稳态模型评估（HOMA）指数作为胰岛素抵抗的衡量指标。
Pro12Ala多态性的携带者和非携带者的FFA循环水平非常相似（0.46±0.2对0.47±0.2，无显著差异）；两组无论有无该多态性，血浆葡萄糖、甘油三酯、HDL胆固醇和血压也相似。为了考虑肥胖可能产生的混杂效应，对超重（BMI≥25 kg/m²）和体重正常者（BMI＜25 kg/m²）进行了单独分析。正如预期的那样，超重者的循环血浆FFA浓度以及甘油三酯、血压和HOMA显著高于体重正常者，但在每个BMI组内，Pro12Ala多态性的携带者和非携带者之间未检测到显著差异（超重组为0.49±0.2对0.48±0.2，无显著差异；体重正常组为0.44±0.2对0.47±0.2，无显著差异）。还按FFA浓度的四分位数递增对Pro12Ala多态性进行了分析，未观察到多态性频率与FFA值之间的关系（总体χ² = 0.48，无显著差异）。
本研究未显示PPARγ基因的Pro12Ala多态性与普通人群空腹FFA之间存在任何关系。不能排除在不同条件下（即餐后）对FFA有不同处理方式的可能性，这仍有待探索。
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