血管紧张素转换酶和p22（phox）基因多态性与西班牙低风险人群冠心病风险的关系

Angiotensin-converting enzyme and p22(phox) polymorphisms and the risk of coronary heart disease in a low-risk Spanish population.

作者信息

Mata-Balaguer Trinidad, de la Herrán Roberto, Ruiz-Rejón Carmelo, Ruiz-Rejón Manuel, Garrido-Ramos Manuel A, Ruiz-Rejón Fernando

机构信息

Departamento de Genética, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain.

出版信息

Int J Cardiol. 2004 Jun;95(2-3):145-51. doi: 10.1016/j.ijcard.2003.05.017.

DOI:10.1016/j.ijcard.2003.05.017

PMID:15193812

Abstract

OBJECTIVE

To evaluate the genetic contribution to myocardial infarction in a homogeneous Caucasian population (a Mediterranean Spanish population) with very low frequency of coronary heart disease (CHD).

DESIGN

We analyzed a total of 210 subjects, younger than 55 years, considered to be a low-risk population (104 cases of myocardial infarction and 106 control), and genotyped them (using polymerase chain reaction and sequencing) for the angiotensin-converting enzyme (ACE) insertion/deletion (ACE I/D) and for the C242T polymorphism of NADPH oxidase p22(phox). Also, we sequenced 23 alleles of the ACE gene (9 D and 14 I) for the region that includes the end of the intron 16 and the exon 17.

RESULTS

The ACE genotype-prevalence values for II, ID and DD were 4.81%, 28.85% and 66.34%, respectively, among the myocardial infarction patients, and 2.83%, 71.70% and 25.47% among controls. The statistical analysis comparing patients and controls revealed significant differences (chi(2)=25.09, P=0.00000055) between the two subpopulations. Also, we found a strong association between the genotype DD and the risk of suffering CHD (odds ratio (OR): 3.64; 95% CI: 2.37-8.07). The prevalence of the CC, TC and TT genotypes of p22(phox) gene among healthy controls proved to be 53.77%, 44.34% and 1.89%, while those of myocardial infarction were 58.65%, 39.42% and 1.93%, respectively. The association of C242T polymorphism of the p22(phox) gene with CHD was not statistically significant, (chi(2)=0.49, P=0.48). Logistic-regression analysis demonstrated that the independent risk factor for developing myocardial infarction was the DD genotype of ACE gene. Finally, our results indicate that alleles I and D of ACE gene are differentiated at three positions (nucleotide sites 14,480, 14,488 and 14,521) of which, the positions 14,480 and 14,488 were in absolute linkage disequilibrium.

CONCLUSIONS

Among subjects of a Mediterranean population with low risk for CHD, the presence of DD ACE genotype could be a risk factor for myocardial infarction, and we confirm the linkage disequilibrium between two nucleotide positions of the ACE gene and the polymorphism for an Alu insertion.

摘要

目的

在冠心病（CHD）发病率极低的同质化白种人群（西班牙地中海人群）中评估基因对心肌梗死的影响。

设计

我们分析了总共210名年龄小于55岁的受试者，他们被视为低风险人群（104例心肌梗死患者和106名对照），并对他们进行基因分型（使用聚合酶链反应和测序），检测血管紧张素转换酶（ACE）插入/缺失（ACE I/D）以及NADPH氧化酶p22(phox)的C242T多态性。此外，我们对ACE基因的23个等位基因（9个D和14个I）进行测序，该区域包括内含子16末端和外显子17。

结果

心肌梗死患者中II、ID和DD的ACE基因型流行率分别为4.81%、28.85%和66.34%，对照组中分别为2.83%、71.70%和25.47%。比较患者和对照组的统计分析显示，两个亚组之间存在显著差异（χ² = 25.09，P = 0.00000055）。此外，我们发现DD基因型与患CHD的风险之间存在强关联（优势比（OR）：3.64；95%置信区间：2.37 - 8.07）。健康对照组中p22(phox)基因CC、TC和TT基因型的流行率分别为53.77%、44.34%和1.89%，而心肌梗死患者中分别为58.65%、39.42%和1.93%。p22(phox)基因C242T多态性与CHD的关联无统计学意义（χ² = 0.49，P = 0.48）。逻辑回归分析表明，发生心肌梗死的独立危险因素是ACE基因的DD基因型。最后，我们的结果表明，ACE基因的I和D等位基因在三个位置（核苷酸位点14480、12488和14521）存在差异，其中，位点12480和14488处于完全连锁不平衡状态。