Estrogen receptor beta genetic variants and combined oral contraceptive use as relates to the risk of hypertension in Chinese women

Background and aims: Estrogen receptor beta (ESR2) plays an important role in cardiovascular physiology and blood pressure regulation, whereas estrogens may influence gene expression, growth, and cellular differentiation in target tissues by activating estrogen receptors. This study aims to investigate the association between common genetic variants of ESR2 gene and the risk of hypertension and to explore the combined effected of ESR2 variants and combined oral contraceptive (COC) use for hypertension risk.

Methods: A population-based case-control study was conducted in 621 female hypertensive patients and 621 female normotensive controls.

Results: ESR2 G1082A heterozygote genotype (GA) was in significant relationship with hypertension (crude odds ratio [OR] = 1.38, 95% CI: 1.09-1.76; adjusted odds ratio [OR] = 1.38, 95% CI: 1.09-1.76). No association was observed for ESR2 G1730A polymorphism. Furthermore, the joint effects of the heterozygote of G1082A polymorphism (heterozygote model: GG/AA vs. GA) and cumulative COC use time ≥15 years significantly increased the risk of hypertension [adjusted odds ratio (OR) = 2.19, 95% CI: 1.49-3.24], and the interaction effects between those two risk factors were significant (p = 0.0001).

Conclusions: The heterozygote GA genotype of ESR2 gene G1082A polymorphism may be a risk genotype for hypertension in Chinese women, and the GA genotype (heterozygote model: GG/AA vs. GA) of G1082A locus together with COC use simultaneously contributed to hypertension development.