A Correlational Study Of The Relationship Between Nuclear Receptor Superfamily NR5A1Gene Mutation And Premature Ovarian Failure In Chinese Han

Background Premature ovarian failure (POF) is defined as the loss of ovarian function for the women before the age of40, due to some kind of factors. This disease is characterized by amenorrhea and the atrophy of sexual organs accompanied with elevated levels of gonadotropins and decrease levels of estrogen. The clinical symptoms are hot flashes and sweating, vaginal dryness and decreased libido before and after amenorrhea. Currently, there are no reliable markers to predict its occurrence, and no effective treatment measures to improve ovarian function, leading to one of the important reasons for infertility. POF seriously affects the patient’s quality of life and brings great suffering to their physical and mental health. Previous studies showed that the incidence of POF was1/100among the women before the age of40and1/1000before the age of30. Recently, the incidence of POF is rising and this disease shows a very obvious low aging tendency.POF is clinically highly heterogeneous and the etiologies are mixed and unclear. It has been reported that the etiologies involve genetic, immune, iatrogenic and environmental factors, but most etiologies are unclear and POF is idiopathic. It was reported that genetic factors could account for40%of the causes. However, early analysis of large sample POF karyotype showed that the abnormal rate for chromosome numbers or structures was only12.1%suggesting that the anomalies of genetic materials occur more in a single gene or at nucleotide level.The nuclear receptor superfamily NR5A1(Steroidogenic factor-1, SF-1) is one of the candidate genes for POF. Previous experiments demonstrated that the phenotype of Nr5al-/-mouse was similar to human adrenal insufficiency and46, XY complete gonadal dysplasia. Previous experiments demonstrated that there was a correlation between NR5A1gene and ovarian reserve. Currently, the relevance of NR5A1gene mutations to POF among Chinese Han has not been reported.Objective Screening the mutation of NR5A1gene among POF patients in a large sample of Chinese Han. Analyze the relevance of NR5A1gene mutation to POF with POF.Methods:384patients who were suffering from POF from reproductive hospital affiliated to Shandong University were chosen as the experimental subjects. Another376healthy women with normal function of ovarian were chosen as the control. Peripheral blood from patients with POF and controls was collected and genomic DNA for all the samples was extracted. PCR was used to amplify six exons of NR5A1gene and the corresponding flanking sequences. PCR amplication products were all sequenced and these sequences were all analyzed to determine if sequence mutations exist.Results1) One patient carried a missense mutation which was located at exon2c.13T>G. For this mutation, tyrosine was mutated into aspartic acid. However, there was no such mutation in control group.2) we found two known SNP sites:rs1110061(exon4) and rs2297605(exon5).Conclusions The mutation of NR5A1gene is one possible reason for POF among Chinese woman and further study should be performed to understand its pathogenic mechanism.