González Sánchez J L, Serrano Ríos M, Fernández Perez C, Laakso M, Martínez Larrad M T
Department of Internal Medicine II, Hospital Universitario Clínico San Carlos, Madrid, Spain.
Eur J Endocrinol. 2002 Oct;147(4):495-501. doi: 10.1530/eje.0.1470495.
To investigate the role of the Pro12Ala peroxisome proliferator-activated receptor (PPAR) gamma-2 polymorphism in the susceptibility to the insulin resistance syndrome and its metabolic complications in a population-based nationwide multicenter study in Spain.
464 unrelated adults (45.3% men and 54.7% women) aged between 35 and 64 years were randomly chosen from a nationwide population-based survey of obesity and related conditions including insulin resistance and cardiovascular risk factors.
Anthropometric determinations included: body mass index (BMI), waist-to-hip ratio, sagittal abdominal diameter; biochemical determinations included: fasting plasma glucose concentration and concentration 2 h after an oral glucose tolerance test (OGTT), total cholesterol, high and low density lipoprotein-cholesterol, triglycerides, leptin and insulin. Systolic and diastolic blood pressure were also measured. Genotyping of the PPARgamma-2 Pro12Ala polymorphism was determined by polymerase chain reaction and single strand conformation polymorphism analysis.
The Ala12 allele frequency was higher in obese men than in lean men (0.15 vs 0.08, P=0.03). Men carriers of the Ala12 allele had a higher BMI than non-carriers (38.9% vs 21.3%; adjusted odds ratio 2.36, 95% confidence interval 1.10-5.05, P=0.03). However, despite higher BMI obese men carriers of the Ala12 allele had lower sagittal abdominal diameter than Pro12 homozygotes (24.1+/-3.2 vs 26.3+/-2.5 cm, P=0.01). The Ala12 allele was associated with lower total triglycerides levels in the overall population and it was also associated with lower fasting insulin levels and a higher insulin sensitivity by homeostasis model assessment (HOMA) in women.
Our results suggest that the Pro12Ala polymorphism of the PPARgamma-2 gene promotes peripheral deposition of adipose tissue and increased insulin sensitivity for a given BMI. The results in women might be due to their different adipose tissue distribution.
在西班牙一项基于全国人群的多中心研究中，调查过氧化物酶体增殖物激活受体（PPAR）γ-2基因Pro12Ala多态性在胰岛素抵抗综合征及其代谢并发症易感性中的作用。
从一项基于全国人群的肥胖及相关疾病（包括胰岛素抵抗和心血管危险因素）调查中，随机选取464名年龄在35至64岁之间的无亲缘关系成年人（男性占45.3%，女性占54.7%）。
人体测量指标包括：体重指数（BMI）、腰臀比、腹矢状径；生化指标包括：空腹血糖浓度及口服葡萄糖耐量试验（OGTT）后2小时血糖浓度、总胆固醇、高密度和低密度脂蛋白胆固醇、甘油三酯、瘦素和胰岛素。还测量了收缩压和舒张压。通过聚合酶链反应和单链构象多态性分析确定PPARγ-2基因Pro12Ala多态性的基因分型。
肥胖男性中Ala12等位基因频率高于瘦男性（0.15对0.08，P = 0.03）。携带Ala12等位基因的男性BMI高于非携带者（38.9%对21.3%；校正优势比2.36，95%置信区间1.10 - 5.05，P = 0.03）。然而，尽管BMI较高，但携带Ala12等位基因的肥胖男性腹矢状径低于Pro12纯合子（24.1±3.2对26.3±2.5厘米，P = 0.01）。在总体人群中，Ala12等位基因与较低的总甘油三酯水平相关，在女性中还与较低的空腹胰岛素水平及通过稳态模型评估（HOMA）得出的较高胰岛素敏感性相关。
我们的结果表明，PPARγ-2基因的Pro12Ala多态性促进脂肪组织在外周沉积，并在给定BMI情况下增加胰岛素敏感性。女性中的结果可能归因于她们不同的脂肪组织分布。
