P-207: Pharmacogenetic Study of CYP19A1 (Aromatase) in Ovarian Induction in Iranian Polycystic Ovarian Syndrome Patients

Background: Hyper-androgenemia is one of the main clinical features of polycystic ovarian syndrome (PCOS). Letrozol is an aromatase inhibitor drug, which is co-administered with gonadotropins in most cases of PCOS, to improve ovulation. Aromatase has a critical role in catalyzing the conversion of androgens to estrogens and is responsible for keeping the homeostatic balance between them. Hence variations in its gene, CYP19A1, might be associated to syndromes of androgen excess such as PCOS. Materials and Methods: The aim of our study was to investigate polymorphisms of CYP19A1 gene in PCOS patients (55 people). The comparison was against 2 control groups which included 40 healthy fertile women and 45 women (with male factor infertility) under intra uterine insemination (IUI) treatment (drug response-control group). The study investigated the associations between above three groups and observed SNPs of CYP19. The expressions of CYP19A1 mRNA and protein in patients who had reached IVF treatment cycle was studied to compare with the observed polymorphisms. Results: PCR- RFLP was undertaken (exons 7, 9 and 10) on extracted DNA from blood samples to detect known functional polymorphisms of CYP19A1. Alterations of amino acids in the active site of exon 8, a TCT ins/del and a polymorphic TTTA repeat in intron 4 were also studied by sequencing. Finally the mRNA and protein expressions of 5 PCOS patients in comparison to 5 drug response-control patients was studied with real time and western blot techniques, respectively. Conclusion: No association was observed between SNPs of exons 7, 9 and 10 with PCOS. However, an association between polymorphism rs700519 in exon 7 and improvement of treatment (Follicular Diameter) was seen in cases who had taken Letrozol. No amino acid changes were observed in the active site of this gene. In addition, more studies must be done on the expression of CYP19A1 gene in both mRNA and protein levels.