The Associatin Between Gene Polymorphisms Of Microsomal Epoxide Hydrolase Gene And The Susceptivity Of Polysistic Ovary Syndrome

Background Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome with different degrees of reproductive and metabolic abnormalies. The clinical manifestation shows a highly heterogenic disorder, such as, oligomenorrhea, amenorrhea, hirsutism, acne, obesity, etc. It affects 5%-10% of reproductive-age women in China. The cause of PCOS is complicated. The features, familial clustering of PCOS cases and the patients from different races or areas show different clinical features. Investigators in the world speculated that the interaction between multiple genetic factors and environmental factors may be the cause for the morbidity and development of this syndrome. EPHX is a biological enzyme, catalyzing the hydrolysis of a wide range of arene and aliphatic epoxides by trans-addition of water to form glycols. It is accepted that microsomal epoxide hydrolase plays a pivotal role in the metabolism endogenous and exogenous epoxides. The gene encoding microsomal epoxide hydrolase(EPHX) is located at human chromosome 1q4211.It has been reported that two variants (Tyr113His and His139Arg) in the coding regions of this gene are correlated with enzymatic activity.Some researchers have established the associations with some diseases in women reproductive system,such as,pre-eclampsi, ovarian cancer, spontanious abortion,etc. Korhonen S et.al demonstrated that the genetically low activity haplotypeC-G(His113–Arg139) was significantly associated with PCOS. Xinrong Tang et.al suggested that genetype of high-activity EPHX induced by genic mutation may play a role in the protection of PCOS.The EPHX gene is highly expressed on the steroid-hormone producing cells in the human ovary and tests. Researchers has shown that it participates in the metabolism not only of arene and alkin epoxides but also of steroid hormones.For above reasons, this project seeks to find the association between the polymorphisms of microsomal epoxide hydrolase gene and the suspecbility of PCOS. Objective To explore the relationship between susceptibility of polycystic ovary syndrome ( PCOS) and the polymorphisms in EPHX gene in Chinese Han women.Method: A total of 925 unrelated women (636 patients with PCOS and 299 persons for healthy controls) were recruited from the the first affiliated hospital of Anhui Medical University. All recruited people in the study were genetyped by for the 113Tyr→His polymorphisms in exon3 and the139His→Arg polymorphisms in exon4 of the epoxide hydrolase gene by RFLP-PCR, and the enzyme activity was compared in the case group and the control group.Result:Initially, we compared the single point genotype and allele distributions of these SNPs in the PCOS group and control group. Genotype and allele distributions of exon3 and 4 did not reveal significant difference between the groups(P=0.297,P=0.661 and P=0.216,P =0.136). But when we compared the genetype distribution between the two sub-groups: non- and with hypeandrogenism,which was devided with the criterion of T>2.69nmol/ml, the frequence of the exon4 genetype has a signifitantly difference in the two groups(p=0.043). In addition, we compared the genetype distribution between the two sub-groups: non- and with obesity as well, which was devided in the criterion of BMI≥28kg/m2, the frequence of the exon3 genetype has a signifitantly difference in the two groups(p=0.025). Moreover, according to the study of Hassett et al, we devided the enzymatic activity into three groups: high,middle and low, There were no significantly difference among the groups(P=0.645).Conclusions: The research suggests that the variant genotypes of exon3 and 4 polymorphisms of EPHX gene are not associated with the susceptivity of PCOS .However, the gene polymorphisms of exon3 may be associated with the obesity of PCOS, and the gene polymorphisms of exon4 may be associated with the hyperandrogenism of PCOS.