Haplotype-based association of CYB5A gene polymorphisms (rs1790834 and rs1790858) with polycystic ovary syndrome in a south Indian cohort

Background

Cytochrome b5 type A (CYB5A) augments the 17,20-lyase activity of CYP17A1, a crucial enzyme in androgen biosynthesis. A significant contributing factor to polycystic ovarian syndrome (PCOS) is dysregulated androgen production. This study examined the relationship between PCOS susceptibility and the CYB5A polymorphisms rs1790834 and rs1790858 in a population from South India. While CYB5A polymorphisms have been analysed in other diseases, this study is the first to investigate their association with PCOS.

Methods

A case-control study was performed with 194 patients diagnosed with PCOS and 194 age-matched controls. PCR-RFLP was used for genotyping of the rs1790834 and rs1790858 variants. Chi-square tests were used to compare allele frequencies and genotypes. Using Haploview, linkage disequilibrium and haplotype analysis were carried out, and gene-obesity interactions were evaluated through subgroup analysis based on BMI.

Results

No substantial correlation was detected between individual SNP genotypes or alleles and PCOS within the overall population. ANOVA analysis revealed no significant correlation between genotypes and anthropometric parameters (weight, height, BMI). Haplotype analysis also failed to identify any robust association.

Conclusion

While CYB5A plays a role in androgen biosynthesis through modulation of CYP17A1 activity, our results suggest that the studied SNPs may not independently contribute to PCOS susceptibility in this population. The genetic architecture of PCOS likely involves polygenic contributions, and variants in other steroidogenic or metabolic pathway genes may exert a greater influence than CYB5A alone. Larger studies with greater statistical power, multi-ethnic cohorts, genome-wide approaches, and functional validation are needed to clarify the role of CYB5A in PCOS pathogenesis fully.