Impact of CYP27B1 rs10877012 and rs4646536 polymorphisms on genetic susceptibility and biologic outcomes in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is now recognized as a complex trait influenced by genetic factors. Recent studies have investigated the mechanisms linking gene polymorphisms to PCOS clinical phenotypes. The association of CYP27B1 polymorphisms with susceptibility to PCOS and their influence on assisted reproductive technology outcomes among women with PCOS has not been fully explored. A case-control study involved 129 women diagnosed with PCOS and 150 matched controls. SNaPshot assays were applied for SNP genotyping. Statistical analyses were conducted to explore genotypes associated with PCOS risk and to assess whether these genotypes were related to controlled ovarian hyperstimulation (COH) response and in vitro fertilization (IVF) outcomes. After adjusting for age and BMI, the GT genotype of rs10877012 (Adjusted OR = 2.32, 95% CI = 1.03–5.22, P = 0.042) and the AG genotype of rs4646536 (Adjusted OR = 2.29, 95% CI = 1.02–5.15, P = 0.045) remained significantly associated with an increased risk of PCOS. These two loci exhibited nearly complete linkage disequilibrium (D’=1, r² = 0.98), acting as a single inherited haplotypic block. Furthermore, the rs10877012 GG and rs4646536 AA genotypes were associated with a significantly higher frozen blastocyst formation rate compared to the GT and AG genotypes ( P = 0.012). The CYP27B1 rs10877012–rs4646536 haplotypic block is associated with PCOS susceptibility and may influence IVF outcomes. These findings support a potential role for CYP27B1 genetics in PCOS, highlighting the value of assessing this haplotypic block, which warrants further validation in larger independent cohorts.