埃及患者中MTHFR (c677t)和ace (i / d)多态性与高血压和治疗反应的关系

A. Shafik, K. Hemida, M. Seif-ElNasr, H. Ismail
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摘要

高血压是一种众所周知的流行病,是各种心血管、外周血管和肾脏疾病的危险因素。肾素血管紧张素系统(RAS)是高血压最重要的致病机制之一,是其介导的关键成分;血管紧张素转换酶此外,亚甲基四氢叶酸还原酶基因(MTHFR)的突变已被确定与心血管疾病和高血压的风险相关。本病例对照研究旨在探讨ACE (I/D)和MTHFR (C677T)基因多态性与埃及高血压患者高血压易感性和抗高血压药物反应能力的潜在关系。36例高血压患者与14例对照组年龄、性别相匹配。采用聚合酶链反应(PCR)对MTHFR (C677T)和ACE (I/D)多态性进行基因分型。除血亲关系和肥胖外,患者与对照组的人口学及临床特征均无统计学意义(p < 0.05)。对于MTHFR多态性频率,与野生型677CC基因型频率较低的对照相比,总高血压病例中突变等位基因677T的频率显著较高。然而,与野生基因型相比,突变型677TC+TT基因型与高血压风险没有显著相关性。对于ACE基因的多态性,也只显示出DD等位基因频率较高。有趣的是,ACE DD基因型与血压、肥胖和糖尿病有显著关联。最后,在抗高血压药物的反应方面,我们发现,当使用ACE抑制剂治疗时,DD基因型组的反应最好。这些结果表明MTHFR多态性与高血压无关,而ACE DD基因型可能与原发性高血压相关,被认为是高血压的一个潜在危险因素,而且在埃及患者中,MTHFR基因型是ACE抑制剂治疗的最佳反应组。
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ASSOCIATION OF MTHFR (C677T) AND ACE (I/D) POLYMOR-PHISMS WITH HYPERTENSION AND RESPONSE TO TREAT-MENT AMONG EGYPTIAN PATIENTS
Hypertension, a well-known epidemic health disease, is risk factor for various cardiovascular, peripheral vascular and renal diseases. Renin angiotensin system (RAS) being the most important pathogenic mechanism of hypertension is mediated by a key component; the angiotensin converting enzyme (ACE). Moreover, Mutations in the methylenetetrahydrofolate reductase gene (MTHFR) have been established to be associated with the risk of cardiovascular disease as well as hypertension. This case-control study was conducted out to investigate the potential relationship of ACE (I/D) and MTHFR (C677T) gene polymorphisms with hypertension susceptibility and the responsive ability of antihypertensive drugs in Egyptian hypertensive patients. Thirty six patients suffering of high blood pressure were compared with age and sex matching 14 control cases. MTHFR (C677T) and ACE (I/D) polymorphisms were genotyped by polymerase chain reaction (PCR). The demographic and clinical features of patients and control showed no particular significance (p > 0.05) except for the consanguinity and the obesity. For MTHFR polymorphism frequency, total hypertensive cases showed significantly higher frequency rate for the mutant allele 677T compared to controls with a lower frequency of the wild type 677CC genotype. Whereas the mutant 677TC+TT genotypes were not significantly associated with the hypertension risk when compared to the wild genotype among the case group. For ACE gene polymorphism, also showed only higher frequency rates of DD allele. Interestingly, ACE DD genotype showed significant association with blood pressure, obesity and diabetes. Finally in response of the antihypertensive drugs, we found that, the best responsive group is DD genotype group when treated with the ACE inhibitors. These result suggested that the MTHFR polymorphism was not associated with hypertension while the ACE DD genotype may be associated with essential hypertension and considered as a potent risk factor for hypertension and moreover it is the best responsive group when treated with ACE inhibitors in Egyptian patients.
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