The present study was designed to examine whether sex hormone polymorphisms proven by GWAS are associated with endometriosis risk. Unrelated female participants totaling 1376 in number (395 endometriosis patients and 981 controls) were recruited into the study. Nine single-nucleotide polymorphisms (SNPs) which GWAS correlated with circulating levels of sex hormones were genotyped using a TaqMan allelic discrimination assay. FSH-lowering, and LH- and testosterone-heightening polymorphisms of the FSHB promoter (allelic variants A rs11031002 and C rs11031005) exhibit a protective effect for endometriosis (OR = 0.60-0.68). By contrast, the TT haplotype loci that were GWAS correlated with higher FSH levels and lower LH and testosterone concentrations determined an increased risk for endometriosis (OR = 2.03). Endometriosis-involved epistatic interactions were found between eight loci of sex hormone genes (without rs148982377 ZNF789) within twelve genetic simulation models. In silico examination established that 8 disorder-related loci and 80 proxy SNPs are genome variants affecting the expression, splicing, epigenetic and amino acid conformation of the 34 genes which enrich the organic anion transport and secondary carrier transporter pathways. In conclusion, the present study showed that sex hormone polymorphisms proven by GWAS are associated with endometriosis risk and involved in the molecular pathophysiology of the disease due to their functionality.
Keywords: SNP; association; endometriosis; sex hormones.