Leptin receptor gene polymorphisms are associated with adiposity and metabolic alterations in Brazilian individuals
Leptin receptor gene polymorphisms are associated with adiposity and metabolic alterations in Brazilian individuals
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DOI：
10.1590/s0004-27302013000900002
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发表时间：
2013-12-01
期刊：
影响因子：
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通讯作者：
Hirata, Rosario Dominguez Crespo
中科院分区：
文献类型：
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作者：
Oliveira, Raquel de;Cerda, Alvaro;Hirata, Rosario Dominguez Crespo
目的：本研究的目的是调查肥胖和代谢标志物，如瘦素，葡萄糖和脂质，是否受瘦素（LEP）和瘦素受体（LEPR）基因多态性的影响，在我们的人口样本。研究对象和方法：在巴西圣保罗市的两家临床医院随机选择了一组326名高加索-欧洲血统的个体，年龄在30至80岁之间，87名男性和239名女性，148名肥胖者和178名非肥胖者。所有人在初次面谈时都宣称其族裔群体为白色。评估人体测量、体重指数（BMI）和脂肪量。抽取血样用于DNA提取和瘦素、可溶性瘦素受体、葡萄糖和脂质的测量。采用PCR-RFLP方法检测LEP-2548 G> A和LEPR Lys 109 Arg（c.326A>G）、Gln 233 Arg（c.668A>G）和Lys 656 Asn（c.1968G>C）多态性。结果如下：瘦素和血脂升高以及LEPR Arg 223 Arg（GG基因型）与肥胖风险较高相关（p < 0.05），而LEPR Arg 109 Arg（GG基因型）携带者的风险降低（OR：0.38，95%CI：0.19-0.77，p = 0.007）。多元线性回归分析显示，LEPR 223 Arg、腰围增加和瘦素血症之间存在相关性（p < 0.05），而LEPR 109 Arg与高总胆固醇和甘油三酯相关（p < 0.05）。LEPR单倍型3（AGG：109 Lys/233 Arg/656 Lys）携带者肥胖风险增加（OR：2.56，95%CI：1.19-5.49，p = 0.017）。此外，该单倍型与BMI、腰围和瘦素血症增加相关（p < 0.05）。结论：LEPR基因多态性与肥胖、高瘦素血症和致动脉粥样硬化的血脂谱相关，提示其在瘦素抵抗和心血管风险中的潜在作用。此外，LEPR单倍型3赋予我们的人群肥胖症和高瘦素血症的易感性。
Objective: The aim of the study was to investigate whether adiposity and metabolic markers, such as leptin, glucose, and lipids, are influenced by leptin (LEP) and leptin receptor (LEPR) gene polymorphisms in a sample of our population. Subjects and methods: A group of 326 individuals of Caucasian-European descent, aged 30 to 80 years, 87 men and 239 women, 148 obese and 178 non-obese, was randomly selected at two clinical hospitals in the city of Sao Paulo, Brazil. All individuals declared their ethnic group as white during the initial interview. Anthropometric measurements, body mass index (BMI), and fat mass were evaluated. Blood samples were drawn for DNA extraction and measurements of leptin, soluble leptin receptor, glucose, and lipids. LEP -2548G> A and LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) and Lys656Asn (c.1968G>C) polymorphisms were detected by PCR-RFLP. Results: Increased leptin and serum lipids, and LEPR Arg223Arg (GG genotype) were associated with higher risk for obesity (p < 0.05), while reduced risk was found in LEPR Arg109Arg (GG genotype) carriers (OR: 0.38, 95% CI: 0.19-0.77, p = 0.007). Multiple linear regression analysis showed a relationship between LEPR 223Arg, increased waist circumference, and leptinemia (p < 0.05), while LEPR 109Arg was associated with high total cholesterol and triglycerides (p < 0.05). LEPR haplotype 3 (AGG: 109Lys/233Arg/656Lys) carriers have increased risk for obesity (OR: 2.56, 95% CI: 1.19-5.49, p = 0.017). Moreover, this haplotype was associated with increased BMI, waist circumference, and leptinemia (p < 0.05). Conclusions: LEPR polymorphisms are associated with obesity, hyperleptinemia, and atherogenic lipid profile, suggesting their potential role for leptin resistance and cardiovascular risk. Moreover, LEPR haplotype 3 confers susceptibility to adiposity and hyperleptinemia in our population.