The methionine 196 arginine polymorphism of the TNF receptor 2 gene (TNFRSF1B) is not associated with worse outcomes in heart failure

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.

► TNFα contributes to the pathophysiology of CHF. ► A polymorphism in TNFα Receptor-II (the 587G allele) encodes two different amino acids (M196R). ► The 587G allele is associated with greater severity of some inflammatory diseases. ► We demonstrate that the 587G allele is not associated with increased severity of heart failure.