Alvarez R, Reguero J R, Batalla A, Iglesias-Cubero G, Cortina A, Alvarez V, Coto E
Instituto Reina Sofía de Investigación Nefrológica-Laboratorio de Genética Molecular, Hospital Central de Asturias, Oviedo, Spain.
Cardiovasc Res. 1998 Nov;40(2):375-9. doi: 10.1016/s0008-6363(98)00179-5.
To examine the association between coronary artery disease and polymorphisms at the angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) genes.
A total of 181 patients younger than 50 years and 240 controls from the same homogeneous Caucasian population (Asturias, Northern Spain) were genotyped (using polymerase chain reaction) for the ACE insertion/deletion (ACE-I/D) and the AT1R A/C transversion (AT1R-A/C) (3-untranslated region) polymorphisms.
The DD-genotype was at a non-significant higher frequency among patients (50%) than in controls (41%). No difference between the two groups was found for the AT1R-genotypes. Distribution of ACE-genotypes according to AT1R-genotypes showed a significant association between ACE-DD and AT1R-CC and early coronary disease. Among the CC patients 58% were DD, compared to 21% among the controls (p = 0.02; OR = 5.32, 95% CI = 1.45, 19.51). We determined the distribution of these genotypes among the hypertensive and non-hypertensive patients. Frequencies of ACE- or AT1R-genotypes did not differ between the two groups. However, we found an interaction between the DD- and CC-genotypes in the group of normotensives. Among the CC patients, 13% of the hypertensives and 75% of the normotensives were DD (p = 0.014).
Our results indicate a synergistic contribution of ACE and AT1R polymorphisms to the risk of coronary artery disease. This gene-gene interaction could have clinical implications. Approximately 2% of individuals in our population are CC + DD, and the genotyping of both polymorphisms could identify those with a high relative risk for coronary artery disease.
研究冠状动脉疾病与血管紧张素转换酶（ACE）及血管紧张素II 1型受体（AT1R）基因多态性之间的关联。
对来自同一白种人群（西班牙北部阿斯图里亚斯）的181例年龄小于50岁的患者和240例对照进行基因分型（采用聚合酶链反应），检测ACE插入/缺失（ACE-I/D）和AT1R A/C转换（AT1R-A/C）（3'-非翻译区）多态性。
患者中DD基因型的频率（50%）高于对照组（41%），但差异无统计学意义。两组间AT1R基因型无差异。根据AT1R基因型的ACE基因型分布显示，ACE-DD与AT1R-CC及早期冠状动脉疾病之间存在显著关联。CC患者中58%为DD基因型，而对照组中这一比例为21%（p = 0.02；OR = 5.32，95% CI = 1.45，19.51）。我们确定了这些基因型在高血压和非高血压患者中的分布。两组间ACE或AT1R基因型频率无差异。然而，我们发现正常血压组中DD和CC基因型之间存在相互作用。CC患者中，高血压患者的DD基因型比例为13%，正常血压患者为75%（p = 0.014）。
我们的结果表明，ACE和AT1R多态性对冠状动脉疾病风险有协同作用。这种基因-基因相互作用可能具有临床意义。我们人群中约2%的个体为CC + DD基因型，对这两种多态性进行基因分型可识别出冠状动脉疾病相对风险较高的个体。
