Association Between Single Nucleotide Polymorphisms In MicroRNA Binding Target Genes Of IRS-2,CDKN1A And Polycystic Ovary Syndrome

Objective Polycystic ovary syndrome(PCOS) is a common and highly complex endocrine disorder in adolescents and reproductive women, characterized by menstrual irregularities, biochemical or clinical hyperandrogenism, chronic anovulation, polycystic ovaries, and reduced fertility. The impact of this disorder is not just limited to reproductive age, but continues throughout life. The etiology of PCOS is still unclear, but a strong genetic component to the etiology of PCOS is evident and moreover, it is with significant contributions of both genetic and environmental factors. However, due to the phenotypic heterogeneity, environmental confounders, genetic heterogeneity, unknown nature of gene-gene and gene-environment, interactions, small sample size and limitations of commonly used approaches, studies to identify specific contributing genes have yielded only few conclusive results. Micro-RNA can regulate lots of important genes involving the progress of reproductive system. The aim of this study was to analysis the clinical features, and meanwhile, investigate the association between SNPs in micro RNA target sites of IRS2 gene and CDKN1 A gene and PCOS in south Han population of China. Also, potential risk factors of PCOS were evaluated with the aim of providing further rich molecular mechanisms for the etiology and treatment strateges of PCOS.Methods1.A case-control study was adopted. A total of 188 subjects were included in the study, with 148 subjects with PCOS and 40 control subjects. 5ml peripheral whole blood was collected for obtaining genomic DNA.2. All personal information and potential risk factors was collected by questionnaire. Applied ELISA to test the level of serum luteinizing hormone(LH), follicle stimulating hormone(FSH), Estradiol2(E2), Progesterone(P), testosterone(T), Fasting Insulin(FINS) and fasting plasma glucose(FPG). The value of FSH/LH and HOMA-IR index were also calculate.3. Statistical Product and Service Solutions software 13.0 was used to estimate the associations between the analyzed the polymorphisms within micro RNA target sites of IRS2 and CDKN1 A gene and PCOS.Results 1. The basic characteristics of PCOS patients with clinical data were found various. The patients with PCOS met criteria for clinically requirements. In the collected 148 cases of patients with PCOS, FINS in hyperandrogenemia group is significant higher than the non-hyperandrogenemia group; The BMI, PRL, FINS in IR group is significant higher than the non-IR group; The HOMA-IR in BMI-normal group is significant higher than the BMI-abnormal group; The AMH, HOMA-IR in Menstruation abnormal group is significant higher than the Menstruation normal group.2. A total of 7 SNPs in the two genes was detected, including IRS2 gene(rs2289046 and rs1865434), CDK6 gene(rs1059234、rs3176366、rs3176337、rs3176359 and rs74801436).3. There were no significant differences detected in the associations between 7 SNPs and PCOS after adjusting the risk factors in logistic regression model. And within the PCOS wemen, according to HOMA-IR, BMI, T and Menstruation, there were no significant differences in the associations between 7 SNPs and each groups.Conclusions1. The basic characteristics of PCOS patients with clinical data were found various. The patients with PCOS met criteria for clinically requirements. IR is more associated with oligomenorrhea phenomenon. The fat correlation with IR.2.Our results indicate that polymorphisms within micro RNA target sites of IRS2 and CDKN1 A genes may not be associated with genetic susceptibility of PCOS after adjusting the risk factors(age, BMI, FINS etc al) in logistic regression model.