Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Cytokine. 2012 Dec;60(3):838-42. doi: 10.1016/j.cyto.2012.07.035. Epub 2012 Aug 24.
Tumor necrosis factor α (TNFα) may contribute to the pathologic process of congestive heart failure (CHF). TNFα signaling occurs through two receptors; TNFR1 (TNFRSF1A) and TNFRII (TNFRSF1B). In humans a single nucleotide polymorphism (rs1061622 in TNFRSF1B exon 6; T587G) encodes two different amino acids (M196R) in the transmembrane region. The 587G allele is associated with greater severity and/or prevalence of some inflammatory diseases, but its role in CHF in unknown. This study sought to test the hypothesis that the 587G allele is associated with a worse outcome or more severe phenotype in CHF. Peripheral blood DNA was isolated and genotyped from 379 heart failure patients enrolled in a genetic outcome study (GRACE); (44.7% ischemic, 70.4% male, 8.5% black race, age 55.6 ± 11.7 yr (SD), LVEF 24.5 ± 8.3%, NYHA 2.53 ± 0.64). Genotyping was performed by PCR-RFLP. Cardiac function was assessed from medical records at study entry. The distribution of genotypes in this population was 54% T/T, 38.4% G/T and 7.7% G/G. Mean LV ejection fraction (T/T 24.4 ± 8.2, T/G 25.0 ± 8.4, G/G 23.3 ± 8.6, n=352, p=ns) and LV end-diastolic dimensions (T/T 6.57 ± 0.93, T/G 6.53 ± 1.0, G/G 6.57 ± 0.78, n=211, p=ns) were comparable in all groups. Transplant-free survival (median 23 months (range 1-62 months) did not vary by genotype (p=0.95). A lack of effect (p=0.74) on transplant-free survival was also observed in a subset of patients with ischemic heart failure (n=169). The TNFRSF1B 587G allele is not associated with the severity of heart failure phenotype or clinical outcomes in patients with chronic CHF.
肿瘤坏死因子-α（TNFα）可能导致充血性心力衰竭（CHF）的病理过程。TNFα信号通过两种受体发生；TNFR1（TNFRSF1A）和 TNFRII（TNFRSF1B）。在人类中，单核苷酸多态性（TNFRSF1B 外显子 6 中的 rs1061622；T587G）在跨膜区域编码两种不同的氨基酸（M196R）。587G 等位基因与一些炎症性疾病的严重程度和/或患病率增加有关，但它在 CHF 中的作用尚不清楚。这项研究旨在检验假设，即 587G 等位基因与 CHF 中的不良结局或更严重的表型相关。从参加遗传结局研究（GRACE）的 379 名心力衰竭患者中分离外周血 DNA 并进行基因分型；（44.7%缺血性，70.4%男性，8.5%黑人，年龄 55.6±11.7 岁（SD），LVEF 24.5±8.3%，NYHA 2.53±0.64）。基因分型通过 PCR-RFLP 进行。在研究开始时从病历中评估心功能。该人群的基因型分布为 54% T/T、38.4% G/T 和 7.7% G/G。平均左心室射血分数（T/T 24.4±8.2、T/G 25.0±8.4、G/G 23.3±8.6，n=352，p=ns）和左心室舒张末期内径（T/T 6.57±0.93、T/G 6.53±1.0、G/G 6.57±0.78，n=211，p=ns）在所有组中均相似。无移植存活率（中位数 23 个月（范围 1-62 个月）与基因型无关（p=0.95）。在缺血性心力衰竭患者亚组（n=169）中也观察到无移植存活率的缺乏影响（p=0.74）。TNFRSF1B 587G 等位基因与慢性 CHF 患者心力衰竭表型的严重程度或临床结局无关。
