Molecular role of non-exonic variants in CALPAIN 10 gene in polycystic ovarian syndrome in Saudi women

Introduction: Non-diabetic women with polycystic ovarian syndrome (PCOS) often have abnormal insulin regulation. Calpain 10 (CALP10) is a biomarker of type 2 diabetes mellitus, with some of its single-nucleotide polymorphisms (SNPs) influencing PCOS development.

Methods: In this case-control study on 90 women each with and without PCOS, we explored the molecular role of five CALP10 SNPs using biochemical parameters and Sanger sequencing analyses.

Results: Different genetic models, genotypes, and allele frequencies were significantly associated with UCSNP-19 (rs3842570; p=0.01), UCSNP-44 (rs2975760; p=0.009), UCSNP-56 (rs2975762; p<0.0001), and UCSNP-63 (rs5030952; p=0.0003) in women with PCOS. The multiple logistic regression model showed a strong association of CALP10 SNPs with fasting blood glucose (p<0.001). ANOVA showed significant associations with various biochemical parameters such as FSH (p=0.0001) in UCSNP-19 (rs3842570), FI (p=0.002), TG (p=0.01) in UCSNP-56 (rs2975762) and FBG (p=0.001), FI (p=0.004), FSH (p=0.02) & LDLc (p=0.04) in UCSNP-63 (rs5030952) SNPs. Haplotype analysis also revealed significant associations between different combinations of alleles in the studied 5 SNPs in women with PCOS (p<0.05). Generalized multifactor dimensionality reduction analysis showed the best gene-gene interactions among the five SNPs in CALP10I (p<0.05). However, dendrogram and graphical depletion models found no strong association in women with PCOS.

Conclusion: In conclusion, this study confirms rs3842570, rs2975760, rs2975767, and rs5030952 SNPs in CALP10 gene is associated in diagnosed PCOS women in the Saudi Arabia.