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[载脂蛋白E和血管紧张素转换酶基因多态性作为冠心病的危险因素]

[Apolipoprotein E and angiotensin-converting enzyme gene polymorphisms as risk factors of coronary disease].

作者信息

Bennouar N, Allami A, Laraqui A, Azeddoug H, El-Kadiri N, Benkouka F, Bendriss A, Ghannam R, Benomar A, Fellat S, Benomar M

机构信息

Laboratoire de la ligue cardiovasculaire, Hôpital Ibn-Sina, Rabat, Morocco.

出版信息

Ann Biol Clin (Paris). 2004 May-Jun;62(3):295-304.

PMID:15217762
Abstract

The objective of this study was to test the hypothesis that apo E (RFLP, HhaI) and/or angiotensin-converting enzyme (ACE) (ins16del) are associated with higher risk for coronary heart disease. We investigated 250 patients who underwent complete cardiac examination comprising coronary angioplasty and biological analysis (CT, HDLc, LDLc, TG, apo A and apo B). Prevalence of the alleles of apo E and ACE was assessed by molecular analysis. Patients without stenosis or with non-significant stenosis (> 50% of the vascular lumen) were used as reference group (141 patients). Those presenting a significant stenosis of the coronary artery (. 50% of the vascular lumen) were considered as cases (109 patients). The relative frequency of the e 4 allele was significantly higher in cases than in reference group (p > 0.02). A strong association have been found between coronary heart disease and apo E polymorphism (2 = 8.91; p > 0.05). The presence of the e 4 allele increase the risk of atherosclerosis (RR = 2.71; IC95%: 1.25-5.90; p > 0.02) compared to e 3 allele. Also, subjects with D allele were more frequent in cases than in reference group (p > 0.001). A significant association was noted between ACE polymorphism and coronary heart disease (2 = 42.15; p > 0.001). This relationship was positive (rho de Spearman = 0.39; p > 0.01). With D/D homozygotes patients, the RR for coronary heart disease was 19.10 (p > 0.001), while The RR with I/D heterozygotes was 6.91 (p > 0.001) compared to I/I homozygotes. A significant interaction have been shown up between D/D genotype and arterial hypertension (HTA) (2 de Wald = 16.10; p > 0.001). The multivariate analysis showed that the chronic smoking, diabetes, hypoapolipoproteinemia A, interactive effects between D/D and HTA, I/D and obesity, and between D/D and hypertriglyceridemia were the major significant factors to take into consideration in our population. We also note that subjects with both D and e 4 alleles were presenting a high risk to coronary heart disease (RR = 5.93; IC95%: 2.00-17.55; p > 0.01). Thus, those two alleles (4 and D) appears to be important cardiovascular risk factors in the moroccan population.

摘要

本研究的目的是检验载脂蛋白E(RFLP,HhaI)和/或血管紧张素转换酶(ACE)(ins16del)与冠心病风险较高相关的假设。我们调查了250例接受了包括冠状动脉成形术和生物学分析(CT、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、甘油三酯、载脂蛋白A和载脂蛋白B)在内的完整心脏检查的患者。通过分子分析评估载脂蛋白E和ACE等位基因的患病率。无狭窄或狭窄不显著(血管腔>50%)的患者作为参照组(141例患者)。冠状动脉出现显著狭窄(血管腔≤50%)的患者被视为病例组(109例患者)。病例组中e4等位基因的相对频率显著高于参照组(p<0.02)。已发现冠心病与载脂蛋白E多态性之间存在强关联(χ2 = 8.91;p<0.05)。与e3等位基因相比,e4等位基因的存在增加了动脉粥样硬化风险(相对风险 = 2.71;95%置信区间:1.25 - 5.90;p<0.02)。此外,病例组中携带D等位基因的受试者比参照组更常见(p<0.001)。注意到ACE多态性与冠心病之间存在显著关联(χ2 = 42.15;p<0.001)。这种关系是正相关(Spearman相关系数 = 0.39;p<0.01)。对于D/D纯合子患者,冠心病的相对风险为19.10(p<0.001),而与I/I纯合子相比,I/D杂合子的相对风险为6.91(p<0.001)。已显示D/D基因型与动脉高血压(HTA)之间存在显著相互作用(Wald检验χ2 = 16.10;p<0.001)。多变量分析表明,在我们的人群中,长期吸烟、糖尿病、载脂蛋白A低下、D/D与HTA之间的交互作用、I/D与肥胖之间以及D/D与高甘油三酯血症之间的交互作用是主要的重要因素。我们还注意到同时携带D和e4等位基因的受试者患冠心病的风险较高(相对风险 = 5.93;95%置信区间:2.00 - 17.55;p<0.01)。因此,这两个等位基因(4和D)似乎是摩洛哥人群中重要的心血管危险因素。

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