Study On FSHR Gene Polymorphism And INSR And TOX - 3 Gene Methylation In PCOS Patients

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting6-12%women of reproductive age. About75%of patients with PCOS infertility, therefore it becomes a threat to women’s reproductivehealth ills.PCOS patients show the lack of hypothalamus-pituitary-ovarian axis balance and systemic metabolic disorders.The typical clinical features of PCOS is irregular menstruation, chronic failure to ovulate, obesity, hirsutism, hyperandrogenism, some accompanied by metabolic abnormalities. At the same time, PCOS showed clinical heterogeneity, it not only affects reproductive health, but also cause long-term complications of diabetes, hypertension, and endometrial cancer.Based on the feature of hereditary characteristics and heterogeneity, it strongly suggests PCOS is generated by the combined effect of both genetic and environmental.However, since the limit of the techniques and low fertility and other objective factors, the etiology of PCOS has been making slow progress in studies.PCOS has significant familial aggregation, and easy to occur in the first-degree relatives, which suggests that the genetic factors is an important factor in its etiology. After decades of research, there are more than100candidate genes have been found. Genome-wide association analysis (GWAS) has also been used to the PCOS study. The specific gene exactly related with PCOS has yet to find,and there was few consistent conclusions.Epigenetics can alter gene expression without changing in the DNA sequence. Abnormal epigenetic modifications involved in a variety of diseases. It may be the media between the diseases and environment. Unlike DNA changes, many epigenetic changes are reversible, which provides for the treatment of diseases optimistic about the prospects. Until now, reports on the relation between PCOS and DNA methylation are rare. It has great research potential.In the present study, we try to explore the etiology of PCOS from gene polymorphism and epigenetics perspectives respectively, expecting to make progress in clarifying the pathogenesis of PCOS Association study between FSHR Ala307Thr and Ser680Asn variants and PCOS One important manifestation of PCOS is hypothalamic-pituitary-ovarian axis dysfunction. Follicle stimulating hormone (FSH) is very important hormone in male and female body, regulates the development, growth, mature adolescence, as well as a series of physiological reproductive process. The physiological function of FSH is mediated by follicle stimulating hormone receptor (FSHR) on target cell membrane. Therefore, the stability of the FSHR protein function is closely related to the play of FSH biological functions, FSHR gene mutations and single nucleotide polymorphisms affect gonadal function is bound to a great extent.Based on this, we analyzed the difference of the two most common SNP (rs6165, rs6166) genotype frequencies and allele frequency distribution in the the PCOS case group and the control group in the FSHR gene and do haplotype analysis,in order to verify whether these two SNPs in the FSHR PCOS susceptibility loci.We collect unrelated northern Chinese Han384PCOS patients and768healthy blood samples extracted from peripheral DNA samples through DNA extraction kit. The use of ABI Prism3130Genetic Analysis Platform type FSHR two SNP genotyping, and do haplotype analysis.The results show that the two SNPs of the FSHR gene have high frequency, no significant difference in gene frequency in PCOS cases and controls, and haplotype frequencies in cases and controls were also no significant difference. The two SNPs of FSHR gene may not be PCOS major factor in Northern Han Chinese women.Study of INSR gene, TOX-3gene promoter methylation in PCOS patientsEpigenetics can alter gene expression without changing in the DNA sequence. It may be the media between the diseases and environment. DNA methylation is the most common and most important kind of epigenetic modification.It is covalent modification after DNA replication, which is closed related with multifactorial disease and a variety of complex syndrome.Epigenetics may be the key to the pathogen of PCOS. Until now, reports on the relation between PCOS and DNA methylation are rare. Candidate genes are usually found based on the clinical features of PCOS.We selected INSR genes and TOX-3gene as target. A total of32unrelated PCOS patients and32health control were recruited from Shaanxi in North China. MassARRAY EpiTYPER DNA methylation quantitative analysis technique was used to detect INSR gene and TOX-3gene promoter region methylation.The results showed that the INSR and TOX-3gene promoter methylation level is relatively low, so their transcription is not inhibited by DNA methylation. The quartile and average of INSR and TOX-3gene promoter methylation level are the same or similar between case and control groups.The methylation level of The INSR TOX-3gene promoter region showed no significant differences between the case and control groups.Therefore, the etiology of PCOS may not INSR and TOX-3gene promoter methylation abnormalities.