Unraveling the Role of Cathepsin B Variants in Polycystic Ovary Syndrome: Insights from a Case-Control Study and Computational Analyses.

Polycystic ovary syndrome (PCOS) occurs in women of reproductive age, impairing reproductive and metabolic processes. Variations in the cathepsin B (CTSB) gene can influence the disease prognosis by changing the activity, stability, or expression. These single-nucleotide polymorphisms (SNPs) can affect critical cellular functions like the deposition of extracellular matrix, inflammation, and tissue repair, leading to the development of multifactorial diseases. Our study aims to investigate the association between PCOS risk and CTSB SNPs. In this case-control study, 150 PCOS cases and 150 healthy women were enrolled. Genotyping was conducted using the PCR-RFLP method. Different computational databases were used to predict the impact of variations on the splicing sites. Regarding rs12898, the codominant homozygous (GG vs. AA) and recessive (GG vs. AA + AG) inheritance models reduced PCOS risk by 72% and 71%, respectively. PCOS risk was increased by 2.81, 2.94, 1.62, and 2.20 folds in the codominant (TT vs. CC), recessive (TT vs. CC + CT), T vs. C (rs8898), and T vs. C (rs3779659) modes, respectively. Based on haplotype analysis, ATC and ACT haplotypes significantly enhance PCOS risk by 1.57 and 3.34 folds, respectively. Furthermore, the interaction analysis indicated that AG/TT/CC and AA/TT/CC genotype combinations strongly correlated with high PCOS risks by 2.59 and 4.20 folds, respectively. The CTSB rs12898 G > A and rs8898 C > T can potentially create or disrupt binding sites for several splicing factors. CTSB rs12898, rs8898, and rs3779659 SNPs were associated with PCOS risk in our population. Larger sample sizes will be necessary to confirm these findings and investigate other potential causal factors involved in PCOS etiology.