Gene variation in resistant hypertension: multilocus analysis of the angiotensin 1-converting enzyme, angiotensinogen, and endothelial nitric oxide synthase genes.
Gene variation in resistant hypertension: multilocus analysis of the angiotensin 1-converting enzyme, angiotensinogen, and endothelial nitric oxide synthase genes.
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DOI：
10.1089/dna.2010.1156
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发表时间：
2011-07
影响因子：
3.1
通讯作者：
J. Yugar-Toledo;J. F. Martin;J. Krieger;A. Pereira;Caroline Demacq;O. Coelho;E. Pimenta;D. Calhoun;H. M. Júnior
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文献类型：
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作者：
J. Yugar-Toledo;J. F. Martin;J. Krieger;A. Pereira;Caroline Demacq;O. Coelho;E. Pimenta;D. Calhoun;H. M. Júnior
难治性高血压是一种复杂的多因素高血压病，由遗传和环境因素触发，涉及多个生理途径。单个遗传变异可能不会揭示与顽固性高血压的显着关联，因为它们的影响可能取决于基因-基因或基因-环境相互作用。我们研究了血管紧张素I转换酶（ACE）、血管紧张素原（AGT）和内皮型一氧化氮合酶（NOS 3）多态性与环境因素的相互作用。（性别、年龄、体重指数、甘油三酯、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯、估计肾小球滤过率和尿钠排泄），80名控制良好的高血压患者和70名血压正常的对照者。对所有受试者进行ACE插入/缺失（rs 1799752）、AGT M235 T（rs699）和NOS 3 Glu 298 Asp（rs 1799983）基因分型。使用两种统计方法测试多因素关联：传统的参数方法（调整逻辑回归分析）和多因素降维分析评估的基因-基因和基因-环境相互作用。虽然经校正的logistic回归分析发现，研究的多态性和控制或顽固性高血压之间没有显着关联，多因素降维分析显示，AGT 235 T等位基因携带者患顽固性高血压的风险增加，特别是如果他们年龄超过50岁。AGT 235 T等位基因是难治性高血压的独立危险因素。
Resistant hypertension, a complex multifactorial hypertensive disease, is triggered by genetic and environmental factors and involves multiple physiological pathways. Single genetic variants may not reveal significant associations with resistant hypertension because their effects may be dependent on gene-gene or gene-environment interactions. We examined the interaction of angiotensin I-converting enzyme (ACE), angiotensinogen (AGT), and endothelial nitric oxide synthase (NOS3) polymorphisms with environmental factors (gender, age, body mass index, glycemia, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, estimated glomerular filtration rate, and urinary sodium excretion) in 70 resistant, 80 well-controlled hypertensive patients, and 70 normotensive controls. All subjects were genotyped for ACE insertion/deletion (rs1799752); AGT M235T (rs699), and NOS3 Glu298Asp (rs 1799983). Multifactorial associations were tested using two statistical methods: the traditional parametric method (adjusted logistic regression analysis) and gene-gene and gene-environment interactions evaluated by multifactor dimensionality reduction analyses. While adjusted logistic regression found no significant association between the studied polymorphisms and controlled or resistant hypertension, the multifactor dimensionality reduction analyses showed that carriers of the AGT 235T allele were at increased risk for resistant hypertension, especially if they were older than 50 years. The AGT 235T allele constituted an independent risk factor for resistant hypertension.