Sex-dependent association of blood pressure with oestrogen receptor genes ERalpha and ERbeta.
BACKGROUND
There is mounting physiological evidence for an important role of the oestrogen receptors, ERalpha and ERbeta, in vasodilatation and the response to vascular injury. In addition, genetic studies have suggested that the genes encoding these receptors may be involved in the genetic regulation of blood pressure. The existence of such sex steroid-related genes may help to explain the observed sex differences in blood pressure.


OBJECTIVE
To investigate the role of the oestrogen receptor genes (ERalpha and ERbeta) in blood pressure variation in women and in men.


METHODS
We performed a genetic association study of the oestrogen receptor genes in 718 unrelated healthy white individuals (386 men and 332 women) from the parental generation of the Victorian Family Heart Study, a general population survey of cardiovascular risk.


METHODS
Participants were genotyped for single nucleotide polymorphisms (SNPs) in ERalpha and ERbeta, and blood pressure phenotypes were compared between genotype groups by analysis of variance.


RESULTS
When genotype groups were compared, men inheriting the 'a' allele of the ERalpha SNP had significantly higher systolic blood pressure than men with other genotypes [127.7 +/-14.3 mmHg (mean +/- SD) compared with 132.4 +/- 16.1 mmHg; P = 0.014)]. In addition, men inheriting the 'b' allele of the ERbeta SNP had significantly higher diastolic blood pressure than men with other genotypes (81.4 +/-8.1 mmHg compared with 84.4 +/- 9.6 mmHg; P = 0.004). No significant associations between the oestrogen receptor genes and blood pressure were detected in women.


CONCLUSIONS
These results suggest that ERalpha and ERbeta may be involved in the genetic regulation of blood pressure in men, that the two genes may have different roles, and that these genes may contribute to the differences in blood pressures between the sexes.
Ellis
Justine A
JA
Department of Physiology, The University of Melbourne, Victoria 3010, Australia. justine@unimelb.edu.au
Infantino
Tania
T
Harrap
Stephen B
SB
D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012727:Sex Characteristics
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta