瘦素受体基因Lys109Arg多态性与上海地区中国人群肥胖的相关性研究

Association of Lysl09Arg polymorphism in leptin receptor gene with obesity in Shanghai Chinese population

目的研究瘦素受体(LepR)基因Lys109Arg多态性与上海地区中国人群肥胖的相关性。方法采用聚合酶链反应-单链构象多态性(PCR-SSCP)方法测定无亲缘关系、且有完整临床资料的232名上海地区中国人群的LepR基因Lys109Arg多态性的基因型,并对130例单纯性肥胖患者LepR基因Lys109Arg基因型与各临床变量的关系进行分析。结果检测到1个点突变,即第326位的核苷酸A→G突变[Lys109Arg,A→G(nt326)],肥胖组与对照组LepR基因Lys109Arg变异的基因型频率和等位基因频率的差异无统计学意义(P值均>0.05)。肥胖组中,携带A等位基因者与携带G等位基因者间收缩压、舒张压、身高、体重、体质指数、腰围、臀围、腰/臀比、空腹血糖、空腹胰岛素、血总胆固醇、血三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和尿酸的差异均无统计学意义(P值均>0.05);进一步按性别分组发现,携带G等位基因的男性亚组的收缩压和臀围均显著高于携带A等位基因的男性亚组(P值均<0.05);而携带G等位基因的女性亚组与携带A等位基因的女性亚组间各临床变量的差异无统计学意义(P值均>0.05)。男性肥胖组中,排除其他因素影响之后,收缩压及臀围仍与LepR基因Lys109Arg多态性显著相关(OR=1.853和2.101,95%CI分别为1.524～2.275和1.364～3.229,P值均<0.05)。结论LepR基因Lys109Arg多态性与中国男性肥胖人群的收缩压和臀围相关。

Objective To investigate the association between Lys109Arg polymorphism in leptin receptor （LepR） gene with metabolism syndrome. Methods The genotypes of Lys109Arg polymorphism in LepR gene were determined by polymerase chain reaction single strand conformation polymorphism（PCR-SSCP） assay in 232 unrelated Chinese subjects, including 130 with simple obesity and 102 non obese controls, whose complete clinical data were available. The clinical data of 130 obese subjects were analyzed in association with the Lys109Arg genotype. Results A point mutation, namely the A to G mutation in nt326 of the LepR gene（Lys109Arg）, was identified in these subjects. No significant difference was observed in the genotype frequency of Lys109Arg polymorphism between the obese and non-obese subjects. In obese subjects, the carriers of the allele A did not show significant differences form the allele G carriers in diastolic and systolic blood pressure, height, body weight, body mass index, waist and hip circumferences and their ratio, fasting blood glucose, total cholesterol, triglyceride, low-and high-density lipoproteins, and uric acid （P 〉 0.05） . In the male obese subjects, the allele G carriers had significantly higher systolic blood pressure than the allele A carriers（ 131.25 ± 8.54 vs 105.02±7.07, P 〈0. 05）, and the former had also greater hip circumference（108.50 ± 2.65 vs 95.50±4.95, P 〈 0.05） . Such differences, however, were not observed in the female obese subjects （P 〉 0.05） . Logistic regression analysis showed that Lys109Arg polymorphism was independently associated with systolic blood pressure and hip circumference in male obese subjects （OR = 1. 853 and 2.101, 95% CI of 1.524-2.275 and 1. 364 -3.229, both P〈0.05 ）. Conclusion Lys109Arg variant in LepR gene is associated with systolic blood pressure and hip circumference in Chinese male obese population. （Shanghai Med J, 2007, 30：894-897）