Fares Fuad, Smith Yoav, Azzam Naiel, Zafrir Barak, Lewis Basil S, Amir Offer
Department of Human Biology, Faculty of Natural Sciences, University of Haifa and Department of Molecular Genetics, Carmel Medical Center, Haifa, Israel.
Genomic Data Analysis Unit, Hadassah Medical School, Hebrew University of Jerusalem, Israel.
J Atr Fibrillation. 2012 Dec 16;5(4):757. doi: 10.4022/jafib.757. eCollection 2012 Dec.
Atrial fibrillation (AF) in patients with heart failure signals poor prognosis. The endothelial nitric oxide synthase (eNOS) enzyme is a key player in the counterregulation of oxidative stress, which is related in part to AF pathogenesis. The purpose of this study was to investigate a possible clinical association in heart failure patients between the presence of exon 7 G894T eNOS polymorphism, known to result in the Glu298Asp protein variant, and the occurrence of AF.
We analyzed the DNA of 344 patients with chronic systolic heart failure for exon 7 G894T eNOS polymorphism, using PCR. Odds ratios for AF were calculated for the homo- and heterozygous G-allele G894T variants relative to the TT variant.
Of the 344 patients, 204 (59%) were homozygous for the G allele, 122 (36%) were heterozygous (GT), and 18 (5%) were homozygous for the T allele. AF episodes were documented in 73 patients (36%) with the GG genotype, in 35 (29%) with GT, and in 2 (11%) with TT. The odds ratio for AF, based on the presence of at least one G allele in the eNOS 894 gene, was 3.96 (95% confidence interval, 1.17‒13.56, p=0.04). Having two G alleles increased the odds ratio to 4.5 (95% confidence interval, 1.0‒20.0, p=0.02).
Patients with systolic heart failure demonstrate strong correlation between AF and the presence of a G allele in the exon 7 G894T eNOS genotype. These findings support the importance of eNOS polymorphism in the pathogenesis of AF in heart failure patients.
心力衰竭患者发生心房颤动（AF）预示预后不良。内皮型一氧化氮合酶（eNOS）是氧化应激对抗调节中的关键因子，氧化应激与AF发病机制部分相关。本研究旨在探讨心力衰竭患者中已知可导致Glu298Asp蛋白变体的外显子7 G894T eNOS基因多态性与AF发生之间可能存在的临床关联。
我们采用聚合酶链反应（PCR）分析了344例慢性收缩性心力衰竭患者的DNA，以检测外显子7 G894T eNOS基因多态性。计算相对于TT变体，G等位基因G894T变体纯合子和杂合子发生AF的比值比。
344例患者中，204例（59%）为G等位基因纯合子，122例（36%）为杂合子（GT），18例（5%）为T等位基因纯合子。GG基因型的73例患者（36%）、GT基因型的35例患者（29%）和TT基因型的2例患者（11%）记录到AF发作。基于eNOS 894基因中至少存在一个G等位基因，AF的比值比为3.96（95%置信区间，1.17‒13.56，p = 0.04）。具有两个G等位基因使比值比增加至4.5（95%置信区间，1.0‒20.0，p = 0.02）。
收缩性心力衰竭患者中，AF与外显子7 G894T eNOS基因型中G等位基因的存在之间存在强相关性。这些发现支持eNOS基因多态性在心力衰竭患者AF发病机制中的重要性。
