Emre Ayse, Sahin Sinan, Erzik Can, Nurkalem Zekeriya, Oz Dilaver, Cirakoglu Beyazit, Yesilcimen Kemal, Ersek Birsen
Department of Cardiology, Siyami Ersek Thoracic and Cardiovascular Surgery Center, Istanbul, Turkey.
Cardiology. 2006;106(1):44-50. doi: 10.1159/000092598. Epub 2006 Apr 10.
Effect of hormone replacement (HRT) therapy on plasma lipoproteins and apolipoproteins, endothelial function and myocardial perfusion in postmenopausal women with estrogen receptor-alpha (ER-alpha) IVS1-397 C/C genotype and established coronary artery disease.
BACKGROUND/AIMS: Associations between various ER-alpha polymorphisms and clinical phenotypes have been studied, including lipid levels and coronary atherosclerosis. We studied 48 postmenopausal women to determine the effect of ER-alpha IVS1-397 polymorphism on the response to treatment with HRT.
The study had a randomized, double-blind, placebo-controlled and crossover design. Patients were divided into two groups according to ER-alpha IVS1-397 polymorphism: CC genotype (n = 9); CT or TT genotype (n = 39). HRT was given continuously for 4 weeks, with 4-week washout periods between the treatment periods. Brachial artery Doppler and Tl-201 scintigraphy were performed at the end of each treatment period.
HRT lowered total cholesterol, LDL-c and Apo-B levels from baseline values (all p < 0.05) and to a similar degree in CC and CT/TT genotype patients. HRT increased estradiol, HDL-c and Apo A-1 levels relative to baseline values, but to a greater degree in CC patients (p = 0.04, 0.05 and 0.04 by ANOVA, respectively). HRT increased peak forearm blood flow, brachial artery diameter during reactive hyperemia and endothelium-dependent dilation in both groups, but to a greater degree in CC patients (p = 0.03, 0.03 and 0.04 by ANOVA, respectively). Summed stress and rest scores were also more markedly reduced in CC patients (p = 0.04 and 0.05, respectively). The increase in estradiol levels was strongly correlated with the improvement in endothelium-dependent dilation (r = 0.66, p < 0.01), which in turn showed negative correlation with summed stress (r = -0.62, p < 0.01) and rest scores (r = -0.52, p < 0.05) in the CC genotype group.
These data suggest that the improvement in endothelium-dependent dilation and the reduction in perfusion abnormalities by increasing estradiol levels with HRT in postmenopausal women with coronary artery disease may differ with respect to different genotypes, the effect being more prominent in those patients with ER-alpha IVS1-397 CC genotype.
激素替代疗法（HRT）对雌激素受体α（ER-α）IVS1-397 C/C基因型且患有冠心病的绝经后女性血浆脂蛋白、载脂蛋白、内皮功能及心肌灌注的影响
背景/目的：已对各种ER-α基因多态性与临床表型之间的关联进行了研究，包括血脂水平和冠状动脉粥样硬化。我们研究了48名绝经后女性，以确定ER-α IVS1-397基因多态性对HRT治疗反应的影响。
本研究采用随机、双盲、安慰剂对照和交叉设计。根据ER-α IVS1-397基因多态性将患者分为两组：CC基因型（n = 9）；CT或TT基因型（n = 39）。HRT持续给药4周，治疗期间之间有4周的洗脱期。在每个治疗期结束时进行肱动脉多普勒检查和Tl-201闪烁显像。
HRT使总胆固醇、低密度脂蛋白胆固醇和载脂蛋白B水平较基线值降低（所有p < 0.05），且CC和CT/TT基因型患者降低程度相似。HRT使雌二醇、高密度脂蛋白胆固醇和载脂蛋白A-1水平相对于基线值升高，但CC患者升高程度更大（方差分析分别为p = 0.04、0.05和0.04）。HRT使两组的前臂血流峰值、反应性充血时的肱动脉直径和内皮依赖性舒张增加，但CC患者增加程度更大（方差分析分别为p = 0.03、0.03和0.04）。CC患者的应激总分和静息总分也更明显降低（分别为p = 0.04和0.05）。雌二醇水平的升高与内皮依赖性舒张的改善密切相关（r = 0.66，p < 0.01），而内皮依赖性舒张在CC基因型组中又与应激总分（r = -0.62，p < 0.01）和静息总分（r = -0.52，p < 0.05）呈负相关。
这些数据表明，在患有冠心病的绝经后女性中，通过HRT提高雌二醇水平来改善内皮依赖性舒张和减少灌注异常，不同基因型可能存在差异，在ER-α IVS1-397 CC基因型患者中效果更显著。
