一级亲属伴有代谢异常疾病的PCOS患者易感基因研究

Study on susceptibility genes of PCOS patients with first-degree relatives with metabolic abnormalities

目的:探讨基因单核苷酸多态性(SNP)与多囊卵巢综合征(PCOS)的相关性。方法:收集2018年1月至2019年12月就诊于新疆医科大学第一附属医院妇科的289例PCOS患者的临床资料。选取其中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Infinium Asian Screening BeadChip Array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。结果: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,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发病有相关性。结论:一级亲属患有代谢性疾病的PCOS患者rs2587885、rs6541017、rs527687、rs683357和rs7060413 SNP位点多态性与PCOS的发病风险具有相关性。

Objective:To explore the relationship between single nucleotide polymorphisms(SNPs)and polycystic ovary syndrome(PCOS).Methods:Collected clinical datas of 289 PCOS patients in the gynecology department of the First Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2019.The Infinium Asian Screening Array chip was used to detect genome-wide SNP of 35 PCOS patients with first-degree relatives who had metabolic abnormalities and 41 healthy people.The susceptibility genes and candidate SNP loci were determined by KEGG enrichment analysis and PPI analysis,then the candidate SNP loci were analyzed by population genetics.Results:A total 1141 difference SNP locis(P≤0.001)were detected by microarray.The susceptible genes and SNP locis GNAO1(rs2587885),PIK3CD(rs6541017)and FGF13(rs527687,rs683357 and rs7060413)were screened by bioinformatics analysis.Population genetic analysis showed that the A allele of SNP rs527687,the G allele of SNP rs683357,A allele of SNP rs6541017,the C allele of SNP rs2587885 and the G allele of SNP rs7060413 were associated with an decreased risk of developing PCOS(P<0.05,OR<1 and 95%CI<1).In the co-dominant,dominant and recessive genetic models,different genotypes of rs527687,rs683357,rs6541017,rs2587885,rs7060413 locis were associated with the risk of developing PCOS whose first-degree relatives had metabolic diseases.Conclusions:The polymorphisms of SNPs(rs2587885,rs6541017,rs527687,rs683357 and rs7060413)of PCOS patients whose first-degree relatives have metabolic diseases are associated with the risk of PCOS.