Sex differences in the relationship between estrogen receptor alpha gene polymorphisms and arterial stiffness in older humans.
BACKGROUND
Increased arterial stiffness is an independent risk factor for cardiovascular disease. The estrogen system (estrogen and estrogen receptor-alpha [ER-alpha]) has potent vasodilator and antiatherosclerotic activity in vascular tissue and therefore was implicated in the regulation of arterial stiffness. We hypothesized that the relationship between arterial stiffness and gene polymorphisms in ER-alpha has a sex-specific component in older humans.


METHODS
Two hundred healthy older subjects, comprised of 85 men and 115 postmenopausal women (men, 66 +/- 5 years old; women, 64 +/- 7 years old; mean +/- SD) participated in a cross-sectional study. We determined the genotypes of single-nucleotide polymorphisms (SNPs) at -401T/C of intron 1 and at 30T/C of exon 1 of ER-alpha, using a TaqMan-polymerase chain reaction method. Arterial stiffness was estimated by brachial-ankle pulse-wave velocity (baPWV).


RESULTS
Polymorphisms of both -401T/C and 30T/C in ER-alpha affected baPWV values in postmenopausal women but did not affect men. The baPWV in women was significantly lower in the CC genotype at both -401T/C and 30T/C than in the TT genotype (both P < .05), and the CC genotype of two SNPs in women was significantly lower than in men.


CONCLUSIONS
The present study suggests that the relationship between arterial stiffness and -401T/C or 30T/C polymorphisms in ER-alpha is different between sexes in older humans. These polymorphisms may be important in the health and clinical care of cardiovascular function and disease in older women.
Hayashi
Koichiro
K
Department of Music, Sapporo Otani College, Sapporo, Hokkaido, Japan.
Maeda
Seiji
S
Iemitsu
Motoyuki
M
Otsuki
Takeshi
T
Sugawara
Jun
J
Tanabe
Takumi
T
Miyauchi
Takashi
T
Kuno
Shinya
S
Ajisaka
Ryuichi
R
Matsuda
Mitsuo
M
D000368:Aged; D000375:Aging / Q000235:genetics* / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D001916:Brachial Artery / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D004548:Elasticity; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005838:Genotype; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012039:Regional Blood Flow / Q000502:physiology; D012727:Sex Characteristics
D047628:Estrogen Receptor alpha