title: Association of estrogen receptor {alpha} genotypes/ haplotypes with carotid intima-media thickness in Taiwanese women.
abstract: The estrogen receptor alpha gene (ESR1) is an important mediator of the atheroprotective effect of estrogen on the vasculature system. We examined the potential associations between common single nucleotide polymorphism (SNP) variants of ESR1 and intima-media thickness (IMT) in carotid arteries, a strong predictor of cardiovascular disease (CVD). A total of 760 study participants (343 men and 407 women), who had undergone a Duplex ultrasonographic examination of carotid artery, were investigated. Measurement of IMT was performed on a 10-mm segment of the common carotid artery (CCA). Fourteen sequence-validated SNPs of high frequency of Oriental origin were selected and genotyped by the method of Light-Cycler-480-assisted real-time polymerase chain reaction (PCR) followed by melting curve analysis. Results from multiple linear regression analyses showed significant associations of SNPs rs2228480 (Ex8+229G>A) and rs3798758 (Ex8+1988C>A) with the carotid IMT values in women but not in men. Women with SNP rs2228480 (Ex8+229G>A) A/A genotype had a 0.048 mm (7.1%) increase in IMT values versus the other genotypes combined (P = .030). In women who carried the rs3798758 (Ex8+1988C>A) CA+AA combined genotypes, their carotid IMT measures were 0.020 mm (2.9%) decreased as compared with those in women who carried C/ C genotype (P = .042). In haplotype analysis, women with the T-A haplotype versus C-C haplotype of combined rs3798577 (Ex8+1264T>C) and rs3798758 (Ex8+1988C>A) were also found to be associated with a decreased IMT value at a borderline significance (P = .057). Some common SNPs in the ESR1 could be important in modulating carotid atherosclerosis and thereby CVD susceptibility in Taiwanese women.
authors.affiliation: Taipei Medical University, Taiwan.
authors.forename: Meei-Maan
authors.initials: MM
authors.lastname: Wu
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Hsieh
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Lien
authors.forename: Wei-Hung
authors.initials: WH
authors.lastname: Chen
authors.forename: Chyi-Huey
authors.initials: CH
authors.lastname: Bai
authors.forename: Hou-Chang
authors.initials: HC
authors.lastname: Chiu
authors.forename: Hsin-Hon
authors.initials: HH
authors.lastname: Chen
authors.forename: Wen-Tin
authors.initials: WT
authors.lastname: Chung
authors.forename: Yuan-Chii
authors.initials: YC
authors.lastname: Lee
authors.forename: Chung Y
authors.initials: CY
authors.lastname: Hsu
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Lin
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chiou
mesh_terms: D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013624:Taiwan; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology*; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000473:pathology*; D014463:Ultrasonography
chemical_list: D047628:Estrogen Receptor alpha