Genetic determinants of Selenium availability, Selenium-response and risk of Polycystic Ovary Syndrome

Abstract

Abstract Selenium is a trace element and its deficiency has been associated with the risk of PCOS, a multifactorial syndrome that affects a large number of women worldwide. Several databases and literature were searched to find out genetic variants of the genes involved in selenium uptake, metabolism and regulation which may be significantly associated with risk of PCOS through Se related pathways. Genes whish require selenium for their biological actions to perform were also shortlisted. A total of eighteen significantly associated genes were identified which were shortlisted among forty-four variants that could play potential role in the PCOS risk among the study population. The genetic variant distribution data was available in-house and was obtained through GWAS study of the North India population. In silico tools were applied to understand the functional impact of these variants. Three variants namely LDLR(rs2228671), TNF (rs1041981), and SAA2 (rs2468844) are strongly associated with PCOS risk and have a functional impact on encoded protein. Certain variants of Se uptake genes such as DIO1, GPX2, TXNRD1, DIO2 GPX3 genes significantly increase or decrease risk of PCOS development. Se transporter gene SELENOP polymorphism rs9686343 with C allele significantly increased PCOS risk. Other potential genes that require selenium for their biological actions are involved in the inflammatory, antioxidant response, and energy homeostasis signaling pathways. Thus genetic variants of the population may affect the Se availability or Se deficiency may modulate the effect of Se-associated genes due to genetic polymorphism. This information may be helpful in dosage adjustment of Se supplementation for a population in order to have maximum benefits.