title: The methionine 196 arginine polymorphism of the TNF receptor 2 gene (TNFRSF1B) is not associated with worse outcomes in heart failure.
abstract: 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.
authors.affiliation: Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. mctiernanc@upmc.edu
authors.forename: Charles F
authors.initials: CF
authors.lastname: McTiernan
authors.forename: Ravi
authors.initials: R
authors.lastname: Ramani
authors.forename: Benjamin
authors.initials: B
authors.lastname: Burkhead
authors.forename: Dennis
authors.initials: D
authors.lastname: McNamara
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D001483:Base Sequence; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006333:Heart Failure / Q000235:genetics* / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human; D014409:Tumor Necrosis Factor-alpha