Gly482Ser基因和载脂蛋白E基因变异与广西永福汉族长寿老人代谢性状的关系

Association of peroxisome proliferators-activated receptor-y coactivator 1 Gly482Ser with apolipoprotein Eand the longevity and metabolic traits of Hans in Guangxi Yongfu

目的研究广西永福汉族长寿人群（年龄〉90岁）中过氧化物酶体增殖物激活受体7辅激活因子l（PPARGCl）基因Gly482Ser变异和载脂蛋白E（ApoE）基因变异的特征性分布规律，并评价Gly482Ser与ApoE基因的相互作用关系。方法基于本课题组2008-2011年在广西永福长寿之乡的现场工作，以长寿区长寿老年人212例（年龄90～105岁）为长寿组，永福无长寿家族史的非长寿人群207例为对照组。通过入户调查，收集长寿相关的体征、血糖、血脂、血压。提取外周血DNA，分型PPARGCl基因Gly482Ser变异和ApoE基因变异，建立基因组和表型相关数据库。通过单因素分析和多因素遗传统计分析，研究基因组变异和长寿及相关代谢性状的相关。结果与对照组比较，长寿组空腹血糖、总胆固醇和低密度脂蛋白胆固醇均低于对照组。Gly482Ser在全部人群中进行分型，Hardy-Weinberg平衡检验表明在各组中都具有较好的人群代表性，多重比较的Bonferroni法校正后，隐性遗传模型GG基因型与长寿无相关性。按ApoE^4等位基因分层分析隐性遗传模型表明，在非ApoEe4等位基因的携带者中，GG基因型与长寿呈正相关，经Bonferroni法校正后，差异有统计学意义（OR=1．72，P〈O．05）。此外，长寿老人中携带GG基因型的空腹血糖低（P〈0．05），高密度脂蛋白胆固醇水平高（P〈O．05）。结论广西永福汉族长寿老人较对照组具有更好的代谢状态，PPARGCl基因Gly482Ser变异GG基因型与长寿呈正相关，其依赖于不携带ApoE基因风险等位基因ε4而存在。

Objective To explore the association of peroxisome proliferators-activated receptor- coactivator-1 （PPARGC1） Gly482Ser with apolipoprotein E （ApoE） variations in longevity （aged above 90 yrs） Hans in Guangxi Yongfu and to explore the potential association between the variations and metabolic traits. Methods Based on our survey in Guangxi Yongfu in 2008-2011, 212 elderly cases （aged 90-105 years ） were included as longevity group and 207 cases without longevity history were included as control group. By household survey, we collected the longevity related parameters, blood glucose, blood lipid, blood pressure and other related metabolic traits. Peripheral blood was collected to extract DNA, the gene variations of Gly482Ser and ApoE were genotyped, and the database with genome and traits information were set up. By univariate analysis and multivariategenetic statistical analysis, the association between the variations and longevity and metabolic traits was assessed. Results Compared with the control group, the levels of fasting blood glucose, total cholesterol and low density lipoprotein were lower in the longevity group. Gly482Ser was genotyped in all samples and fully fulfilled the Hardy-Weinberg equilibrium. After the Bonferroni correction, recessive model failed to find association between GG genotype and longevity. Stratified analyses by ApoEe4 allele revealed that, in the subgroup with no ApoEε4, PPARGC-1 GG genotype was positively associated with longevity in the recessive model, even after Bonferroni correction （OR = 1.72,P〈0.05）. In addition, longevity group with Gly482Ser GG genotype seemed to have relative lower fasting blood glucose （P〈0.05） and higher high density lipoprotein levels （P^0.05）. Conclusions Longevity Hans in Guangxi Yongfu preserve better metabolic state compared with the control group. GG genotype of Gly482Ser in PPARGC-1 is positively associated with longevity, which depends on not carrying the risk allele of ApoEε4.