首页> 外文期刊>British Journal of Clinical Pharmacology >Ten renin-angiotensin system-related gene polymorphisms in maximally treated Canadian Caucasian patients with heart failure.
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Ten renin-angiotensin system-related gene polymorphisms in maximally treated Canadian Caucasian patients with heart failure.

机译:十种与肾素-血管紧张素系统相关的基因多态性在接受最大治疗的加拿大白人心力衰竭患者中得到了应用。

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The progression and pharmacological response of heart failure-affected patients are subject to interindividual variability. It is also acknowledged that the genotype frequency of certain gene polymorphisms varies across different ethnic groups and that a difference in gene polymorphism frequencies between healthy and heart failure patients seems to exist. WHAT THIS STUDY ADDS: This study investigated associations between 10 gene polymorphisms of RAAS-related genes with an individual's susceptibility to heart failure. Our data suggest that the angiotensinogen (AGT) 235 single nucleotide polymorphism (SNP) may be associated with heart failure in our population and that the AGT(M174)-AGT(T235) haplotype, as well as the AGT/angiotensin-converting enzyme (ACE) gene combination, may play an important role in disease predisposition. AIMS: Racial differences in survival outcomes point towards a genetic role in the pathophysiology of heart failure. Furthermore, contemporary evidence links genetics to heart failure (HF) predisposition. We tested for a difference in prevalence of 10 renin-angiotensin-aldosterone system (RAAS)-related gene polymorphisms between a homogenous population of HF patients and healthy controls. METHODS: One hundred and eleven healthy volunteers and 58 HF patients were included in this study. The healthy control group consisted of males aged between 18 and 35 years old. The HF group consisted of patients (89.7% male) who were 63.8 +/- 7.9 years old, were in New York Heart Association (NYHA) class II-III and had a documented left ventricular ejection fraction (LVEF)
机译:关于此主题的已知信息:受心力衰竭影响的患者的病情进展和药理反应会因个体差异而异。还应认识到,某些基因多态性的基因型频率在不同种族之间变化,并且健康和心力衰竭患者之间似乎存在基因多态性的差异。该研究的目的:本研究调查了RAAS相关基因的10个基因多态性与个人对心力衰竭的敏感性之间的关联。我们的数据表明,血管紧张素原(AGT)235单核苷酸多态性(SNP)可能与我们人群中的心力衰竭有关,并且AGT(M174)-AGT(T235)单倍型以及AGT /血管紧张素转化酶( ACE)基因组合,可能在疾病易感性中起重要作用。目的:生存结果中的种族差异表明心力衰竭的病理生理学具有遗传作用。此外,当代证据将遗传学与心力衰竭(HF)易感性联系起来。我们测试了HF患者的同质人群与健康对照组之间10种肾素-血管紧张素-醛固酮系统(RAAS)相关基因多态性的流行率差异。方法:111名健康志愿者和58名HF患者被纳入本研究。健康对照组由年龄在18至35岁之间的男性组成。 HF组由年龄在63.8 +/- 7.9岁,属于纽约心脏协会(NYHA)II-III级且记录在案的左心室射血分数(LVEF)<或= 40%的患者(男性占89.7%)组成在过去的6个月内。尽管已使用血管紧张素转换酶(ACE)抑制剂和β-肾上腺素受体阻滞剂对其病情进行了最大程度的治疗,但它们仍然是有症状的,因此是高度专业化且均一的患者人群。两组均由加拿大高加索人组成。分析的多态性是:ACE(I / D),血管紧张素II受体1型(AGTR1)(A1166C),血管紧张素原(AGT)(M235T和T174M),内皮型一氧化氮合酶(eNOS)(T -786C和Glu298Asp),肾上腺素能受体a2(ADRB2)(Gln27Glu),缓激肽受体β2(BDKRB2)(+ 9 / -9),醛固酮合酶(CYP11B2)(T-344C)和adducin-1( ADD1)(Gly460Trp)。结果发现在我们的HF组中,AGT(T235)等位基因(P = 0.0025,OR 2.02,95%CI 1.24,3.30)更为普遍。 AGT(174M)-AGT(235T)单倍型也与HF表型相关(P = 0.0069)。对基因-基因组合的探索性评估显示,HF组中AGT(T235)/ ACE(D)组合多态性具有指示性关联(P = 0.02,OR 2.12,95%CI 1.11,4.06)。结论:这项研究表明,在我们的人群中,AGT的SNP可能与HF有关,并且AGT / ACE基因的结合可能在疾病易感性中起重要作用。

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