新疆PCOS一级亲属VNTR、TCF7L2、Calpain-10基因多态性及INSR基因甲基化研究

Polycystic ovary syndrome (Polycystic ovary syndrome, PCOS) have been studied. about seventy years, research on the understanding of the PCOS has shifted from the childbearing age women of reproductive dysfunction, evolved into a complex, multiple system of endocrine metabolic disease, not only affect the female reproductive endocrine function, and endometrial cancer and diabetes, cardiovascular disease and the long-term complications, such as lipid metabolism disorders. The occurrence of PCOS is a common genetic and environmental factors, clinical features and varied, the different regions, different nationalities, different ages, different performance, insulin resistance is important in the pathophysiology of the disease, VNTR, INSR, TCF7L2 and Calpain - 10 gene polymorphism and no correlation between the occurrence and development of the disease. This topic using prospective and retrospective study method of PCOS, han in xinjiang and the onset of first-degree relatives investigation, summarize d, han in xinjiang the pathogenesis of PCOS women and first-degree relatives relationship to clarify VNTR, INSR, TCF7L2 and Calpain - 10 genes and han Chinese and uighurs in xinjiang in patients with polycystic ovary syndrome, the relationship between disease to provide basis for prevention and control of the disease.

多囊卵巢综合征 (Polycystic ovary syndrome, PCOS) 的研究历经七十余年，对PCOS的认识已从单纯的育龄期妇女生殖功能障碍，演变为一种复杂、多系统的内分泌代谢疾病，不仅影响女性生殖内分泌功能，而且是发生糖尿病、子宫内膜癌、心血管疾病及脂代谢异常等远期并发症的罪魁。PCOS的发生是遗传和环境因素的共同影响，临床特征多样，不同民族、年龄阶段，遗传表型不尽相同，与基因甲基化相关，胰岛素抵抗是该病重要的病理生理学基础，VNTR、INSR、TCF7L2及Calpain-10基因的多态性与该病的发生、发展密切相关。本课题采用前瞻性及回顾性研究方法，对新疆PCOS维、汉及一级亲属进行调查，总结新疆维、汉PCOS妇女及一级亲属发病的关系，为阐明VNTR、INSR、TCF7L2及Calpain-10基因与新疆汉族、维吾尔族多囊卵巢综合症患者发病的关系，为该病的防治提供线索。

多囊卵巢综合症(PCOS) 是育龄妇女最常见生殖内分泌疾病，是遗传因素和环境因素交互作用的结果，有家族聚集现象，基因甲基化在遗传方面参与了PCOS的发生。本研究围绕着基因单核苷酸多态性与PCOS的相关性,收集了PCOS和正常对照组各289例的临床资料，比较其临床表型特征和代谢特征；同时从患者和对照组中找出一级亲属患有代谢异常性疾病的 35例PCOS 患者和41例健康人群作为研究对象，采用ASA芯片检测全基因组SNP。通过KEGG富集分析和PPI分析确定易感基因和候选SNP位点，候选SNP位点进行群体遗传学分析，找出与PCOS发病相关的易感基因位点；再将一级亲属患有代谢性疾病的PCOS患者和一级亲属VNTR、INSR、TCF7L2及Calpain-10基因多态性与PCOS合并糖代谢异常的关联性研究；用焦磷酸盐法检测INSR基因甲基化的PCOS患者与其一级亲属及对照组的差别。本研究结果提示ASA基因芯片检测总差异SNP位点1141个（p<0.001），生物信息学分析筛选出的易感基因和SNP位点为GNAO1（rs2587885），PIK3CD（rs6541017）和FGF13（rs527687、rs683357和rs7060413）。群体遗传学分析结果显示rs527687位点A等位基因、rs683357位点G等位基因、rs6541017位点A等位基因、rs2587885位点C等位基因、rs7060413位点G等位基因在PCOS组中的频率显著低于对照组（P<0.05时，OR<1且95%CI<1）。在共显性，显性，隐性遗传模型中rs527687、rs683357、rs6541017、rs2587885、rs7060413不同的基因型跟一级亲属有代谢性疾病的PCOS的发病有相关性。PCOS患者INSR基因甲基化与其父亲及对照组9个CPG甲基化基因位点的差异无统计学意义（p>0.05），与其母亲的CPG14甲基化基因位点差异有统计学意义（p<0.05）。因此，本研究提示一级亲属患有代谢性疾病的PCOS患者rs2587885、rs6541017、rs527687、rs683357和rs7060413 SNP位点多态性跟PCOS的发病风险具有相关性。PCOS患者INSR基因位点CPG14甲基化与其母亲有相关性。