Evidence for associations between common polymorphisms of estrogen receptor beta gene with homocysteine and nitric oxide.

BACKGROUND

Homocysteine and asymmetric dimethylarginine (ADMA) affect nitric oxide (NO) concentration, thereby contributing to cardiovascular disease (CVD). Both amino acids can be reduced in vivo by estrogen. Variation in the estrogen receptor (ER) may influence homocysteine and ADMA, yet no information is available on associations with single nucleotide polymorphisms in the estrogen receptor genes ERalpha (PvuII and XbaI) and ERbeta (1730G-->A and cx + 56 G-->A).

OBJECTIVE

To find relationships between common polymorphisms associated with cardiovascular disease and cardiovascular risk factors homocysteine and ADMA.

METHODS

In a cross-sectional study with healthy postmenopausal women (n = 89), homocysteine, ADMA, nitric oxide metabolites (NOx), plasma folate and ERalpha and beta polymorphisms ERalpha PvuII, ERalpha XbaI; ERbeta 1730G-->A (AluI), ERbeta cx + 56 G-->A (Tsp509I) were analyzed.

RESULTS

Women who are homozygotic for ERbetacx + 56 G-->A A/A exhibited higher homocysteine (p = 0.012) and NOx (p = 0.056) levels than wildtype or heterozygotes. NOx concentration was also significantly affected by ERbeta 1730 G -->A polymorphism (p = 0.025). The ERbeta (p < 0.001) and ERalpha (p < 0.001) polymorphisms were in linkage disequilibrium.

CONCLUSIONS

Women who are homozygotic for ERbetacx + 56 G-->A A/A may be at increased risk for cardiovascular disease due to higher homocysteine levels.