多囊卵巢综合征易感基因与代谢表型相关性分析

Correlation analysis between polycystic ovary syndrome susceptibility genes and metabolic phenotypes

目的 探讨多囊卵巢综合征（PCOS）相关易感基因——LHCGR、THADA和DENND1A基因位点多态性与代谢表型的关系及易感基因的致病作用.方法 选择2006至2010年在山东大学附属省立医院生殖医学中心门诊就诊的PCOS患者1489例（PCOS组）,对照组为非PCOS且无代谢异常的不孕患者4 708例;观察PCOS易感基因位点2p16.3（LHCGR基因rs13405728位点）、2p21（THADA基因rs13429458、rs12478601位点）和9q33.3（DENND1A基因rs2479106、rs10818854位点）及各基因多态性位点不同基因型PCOS患者之间的糖代谢及血脂代谢水平的差异.结果 THADA基因rs 12478601位点CC基因型患者血清低密度脂蛋白胆固醇（LDL-C）水平较TC ＋TT基因型者[分别为（2.5±0.8）、（2.4±0.8） mmol/L]升高,差异有统计学意义（P=0.01）;DENND1A基因rs2479106位点GG＋AG基因型者口服葡萄糖耐量试验（OGTT）后2h胰岛素水平高于AA基因型者[分别为（71±65）、（64 ±50） mU/L,P=0.05],患者一级亲属中糖尿病的发生率也明显增加[分别为9.9％ （66/666）、6.9％ （52/751）,P＜0.05];THADA基因rs13429458、DENND1A基因rs10818854、LHCGR基因rs13405728位点与患者代谢表型无显著相关性（P＞0.05）.结论 遗传因素对PCOS患者的临床特点改变有一定影响,THADA基因与PCOS患者脂代谢关系密切,DENND1A基因则可能参与了PCOS患者胰岛素代谢过程,LHCGR基因与PCOS患者代谢表型无明显相关性.

Objective To investigate the relationship between polycystic ovary syndrome （PCOS） susceptibility single nucleotide polymorphisms （SNP） and metabolic phenotypes in glucose and lipid metabolism and explore the pathophysiological mechanism of the susceptibility genes.Methods Three of PCOS susceptibility locus 2p16.3 （rs13405728 of LHCGR gene）,2p21 （rs13429458,rs12478601 of THADA gene） and 9q33.3 （rs2479106,rs10818854 of DENNDIA gene） were selected and the metabolic phenotypes were compared between different genotypes of SNP in PCOS patients （using dominant model）.Results Low-density lipoprotein cholesterol was significantly increased in CC genotype group than in TC ＋ TT groups at rs12478601 of THADA gene [（2.5 ± 0.8）,（2.4 ± 0.8） mmol/L; P =0.01].Serum insulin level of 2 hours after 75 g glucose intake was significantly higher in GG ＋ AG groups than that of AA group at rs2479106 of DENND1A gene[（71 ±65）,（64 ±50） mU/L;P =0.05],and the prevalence of type Ⅱ diabetes in first-degree relatives of patients were also increased [9.9% （66/666）,6.9% （52/751） ; P 〈 0.05].No association was found between metabolic phenotypes and genotypes of rs13429458,rs10818854,and rs13405728.Conclusions Genetic factors probably have effect on the metabolic characteristics of PCOS.THADA gene is related to lipid metabolism,while DENND1A gene may be involved in insulin metabolism in patients with PCOS.