Endogenous Estradiol and Its Association with Estrogen Receptor Gene Polymorphisms

Abstract We evaluated potential associations between single nucleotide polymorphism (SNP) variants of the estrogen receptor genes ESR1 and ESR2 and circulating estradiol (E 2 ) concentrations in women of 4 races/ethnicities. The study population was drawn from participants in the Study of Women's Health Across the Nation (SWAN). A total of 1,538 African American, Caucasian, Chinese, and Japanese women from SWAN participated in the Sex Steroid Hormone Genetics Protocol by providing blood for sex steroid hormone analyses and consenting to lymphocyte transformation from which DNA was extracted and genotyped. We evaluated 4 ESR1 SNPs ( ESR1 rs9340799 , ESR1 rs2234693 , ESR1 rs728524 , and ESR1 rs3798577) , and 3 ESR2 SNPs ( ESR2 rs1255998 , ESR2 rs1256030 , and ESR2 rs1256065 ). Mean E 2 level was 196.0 ± 4.0 pmol/L in women who were premenopausal and perimenopausal (with blood drawn on days 2 through 5 of the menstrual cycle follicular phase); however, mean E 2 levels in Chinese and Japanese women were lower (155.7 ± 10.6 pmol/L and 170.0 ± 10.3 pmol/L, respectively) than in African American (196.4 ± 8.1 pmol/L, P P ESR1 rs3798577 CC genotype was associated with lower circulating E 2 concentrations in African American women ( P 2 concentrations. In Japanese women, the GC genotype of ESR2 rs1255998 was associated with significantly lower circulating E 2 concentrations that explained about 4% of the variation. Circulating E 2 concentrations were not strongly or consistently associated with selected polymorphisms for the estrogen receptor genes. The 2 strongest associations explained 2 concentrations.