AUTHOR=Alageel Arwa A. , Alshammary Amal F. , Ali Khan Imran TITLE=Molecular role of non-exonic variants in CALPAIN 10 gene in polycystic ovarian syndrome in Saudi women JOURNAL=Frontiers in Endocrinology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1303747 DOI=10.3389/fendo.2023.1303747 ISSN=1664-2392 ABSTRACT=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.