Impact of CYP2A6 genetic polymorphism on letrozole efficacy in Iraqi women with polycystic ovary syndrome

Abstract

Objectives: This study investigated the effects of a genetic polymorphism in CYP2A6 (CYP2A6*2, 1799T>A) on the therapeutic response to letrozole in Iraqi women with polycystic ovarian syndrome (PCOS)-induced infertility. Methods: A prospective, single-center, randomized, controlled pragmatic clinical trial was conducted in 94 Iraqi women with PCOS-induced infertility. The ovulation response to letrozole (2.5 mg/day for 5 days) was assessed via ultrasound (follicle size 18 mm) and hormonal assays (follicle-stimulating hormone, luteinizing hormone, estradiol, prolactin, testosterone, and anti- Mu¨ llerian hormone). Genotyping of CYP2A6*2 (1799T>A, rs1801272) was performed using allelespecific PCR on blood-derived DNA, and the distribution of wild-type (AA), heterozygous (AT), and mutant (TT) alleles was recorded. The association between genotype and letrozole efficacy, including follicle size, endometrial thickness, sex hormone levels, and pregnancy incidence, was also evaluated. Results: The wild-type allele (AA) of the CYP2A6*2 gene (1799A>T, rs1801272) was widely distributed in approximately 51 (54.26 %) women with PCOS. Heterozygous alleles (AT) and mutant alleles (TT) were present in 2 (2.13 %) and 41 (43.61 %) women with PCOS, respectively. There was no notable difference between infertile women who did or did not respond to letrozole and those who carried different genotypes (wildtype AA, heterozygous AT, and mutant TT) of CYP2A6 (1799T>A) regarding sex hormones, follicle size, endometrial thickness, or incidence of gestation (P > 0.05). Conclusion: The CYP2A62 (1799T>A) genetic variant was not associated with letrozole efficacy or resistance in Iraqi women with PCOS, suggesting that this polymorphism does not significantly influence therapeutic outcomes.