Epistasis between CYP19A1 and ESR1 polymorphisms is associated with premature ovarian failure

Because an interaction between CYP19A1 and ESR1 may play a key role in determining the level of circulating E2 by way of the hypothalamus-hypophysis-ovarian axis, the effect of single nucleotide polymorphism (SNP)–SNP interactions between CYP19A1 and ESR1 on the development of premature ovarian failure (POF) was investigated by comparing the polymorphisms of 98 patients with POF and 218 matched controls of Korean ethnicity. A significant association with POF risk was found for the combined genetic effect between the CYP19A1 3′untranslated region (UTR) SNP rs10046 (CT+TT) and the intronic ESR1 SNP rs1569788 (CC) genotype (odds ratio = 12.67, 95% confidence interval: 1.61–99.71), and a statistically significant association was also observed between POF and the CYP19A1 3′UTR SNP rs10046 under a dominant model (odds ratio = 2.51, 95% confidence interval: 1.33–4.76), suggesting that epistasis between ESR1 and CYP19A1 may be involved in the regulation of folliculogenesis.