Martínez-Ríos Marco Antonio, Alvarez-León Edith, Totomoch Armando, Angeles Javier, Peña-Duque Marco Antonio, Delgadillo-Rodríguez Hilda, Martínez-Rodríguez Nancy, Ramírez-Fuentes Silvestre, Fragoso José Manuel, Vargas-Alarcón Gilberto
Interventional Cardiology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Exp Mol Pathol. 2014 Aug;97(1):166-70. doi: 10.1016/j.yexmp.2014.06.009. Epub 2014 Jul 1.
The aim of the present study was to establish the role of ACE gene polymorphisms in the risk of developing in-stent restenosis and/or coronary artery disease (CAD). Eight ACE gene polymorphisms were genotyped by 5' exonuclease TaqMan genotyping assays in 236 patients with CAD who underwent coronary artery stenting. Basal and procedure coronary angiographies were analyzed searching for angiographic predictors of restenosis and follow-up angiography was analyzed looking for binary restenosis. A group of 455 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. Haplotypes were constructed after linkage disequilibrium analysis. Distribution of ACE polymorphisms was similar in patients with and without restenosis. Similar results were observed when the analysis was made comparing the whole group of patients (with and without restenosis) and healthy controls. Six out of eight polymorphisms were in high linkage disequilibrium and were included in five haplotypes (AAAGCA, GGGATG, GAGATG, AGAGCA and AAGACA). The distribution of these haplotypes was similar in patients with and without restenosis. However, CAD patients showed an increased frequency of the AAAGCA haplotype (OR=1.31, 95% CI: 1.04-1.66, P=0.018) and decreased frequencies of GAGATG (OR=0.47, 95% CI: 0.25-0.88, P=0.011) and AGAGCA (OR=0.15, 95% CI: 0.02-0.65, P=0.002) haplotypes when compared to healthy controls. Haplotypes of the ACE gene could be a genetic factor related to coronary artery disease in the Mexican individuals, but do not support its role as a risk factor for developing restenosis after coronary stenting.
本研究的目的是确定ACE基因多态性在支架内再狭窄和/或冠状动脉疾病(CAD)发生风险中的作用。通过5'核酸外切酶TaqMan基因分型检测法,对236例接受冠状动脉支架置入术的CAD患者的8种ACE基因多态性进行基因分型。分析基础冠状动脉造影和手术冠状动脉造影,寻找再狭窄的血管造影预测指标,并分析随访血管造影以寻找二元再狭窄情况。纳入455名无心血管疾病临床和家族史的个体作为对照。在连锁不平衡分析后构建单倍型。有再狭窄和无再狭窄患者的ACE多态性分布相似。在比较整个患者组(有和无再狭窄)与健康对照时,观察到了相似的结果。8种多态性中有6种处于高度连锁不平衡状态,并被纳入5种单倍型(AAAGCA、GGGATG、GAGATG、AGAGCA和AAGACA)。这些单倍型在有再狭窄和无再狭窄患者中的分布相似。然而,与健康对照相比,CAD患者中AAAGCA单倍型的频率增加(OR = 1.31,95% CI:1.04 - 1.66,P = 0.018),而GAGATG(OR = 0.47,95% CI:0.25 - 0.88,P = 0.011)和AGAGCA(OR = 0.15,95% CI:0.02 - 0.65,P = 0.002)单倍型的频率降低。ACE基因的单倍型可能是墨西哥人群中与冠状动脉疾病相关的遗传因素,但不支持其作为冠状动脉支架置入术后再狭窄危险因素的作用。