Journal of Molecular Medicine

, Volume 79, Issue 2, pp 109–115

Tumor necrosis factor receptor 2 gene (TNFRSF1B) in genetic basis of coronary artery disease

  • Adam V. Benjafield
  • Xing Li Wang
  • Brian J. Morris
Original Article

DOI: 10.1007/s001090000168

Cite this article as:
Benjafield, A., Wang, X. & Morris, B. J Mol Med (2001) 79: 109. doi:10.1007/s001090000168

Abstract

Tumor necrosis factor (TNF)-α has been implicated in pathophysiological processes in coronary artery disease (CAD). TNF receptor 2 is of particular interest in mediating such effects. The gene for this receptor (TNFRSF1B) has, moreover, been implicated in hypertension, elevated cholesterol and insulin resistance. TNFRSF1B is thus a worthy candidate in studies of the genetic basis of CAD. We therefore conducted a case-control study of a microsatellite marker with five alleles (CA13-CA17) in intron 4 of TNFRSF1B in 1006 well-characterized white patients with angiographically confirmed CAD and a control group of 183 healthy subjects. We found a strong association of the TNFRSF1B marker with CAD (χ2=40, P=0.00000069). The frequency of the CA16 allele was 33% in CAD vs. 21% in control (odds ratio, OR, to have CAD for presence vs. absence of CA16 allele in CA16 homozygotes was 4.5, 95% CI 2.1–9.4, P<0.0001; in CA16 heterozygotes or was 1.3, 95% CI 0.94–1.89, P=0.10). The frequency of the major allele (CA15) was 43% in CAD vs. 56% in controls (in CA15 homozygotes OR 0.33, 95% CI 0.20–0.52, P<0.0001; in heterozygotes OR 0.41, 95% CI 0.26–0.63, P<0.0001). In a stepwise logistic regression model the CA16 allele was significantly associated with overweight (OR 1.44, 95% CI 1.0–1.9, P=0.027). Apolipoprotein A-I was elevated (P<0.0001), as was high-density lipoprotein (P=0.098), and severity of angina was decreased (P=0.024) as a function of genotype. Plasma soluble (s) TNF-R2 was 5.1±0.1 ng/ml in CAD vs. 3.2±0.1 in control (P<0.0001), 5.2±0.1 in the presence vs. 4.6±0.2 in the absence of vessel disease (P=0.009), and rose with increasing severity of angina: 4.2±0.2 (no angina), 5.0±0.1 (stable angina), 5.4±0.2 (unstable angina; P=0.003). sTNF-R2 was correlated with age, cholesterol, creatinine, fibrinogen, transforming growth factor β and homocysteine and was influenced by TNFRSF1B genotype. Thus genetic variation in or near the TNFRSF1B locus may predispose to CAD.

Tumor necrosis factor receptor Tumor necrosis factor receptor superfamily member 1B gene Coronary artery disease Genetic polymorphism Case-control study 

Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • Adam V. Benjafield
    • 1
  • Xing Li Wang
    • 2
  • Brian J. Morris
    • 1
  1. 1.Basic & Clinical Genomics Laboratory, Department of Physiology and Institute for Biomedical Research, Building F13, The University of Sydney, Sydney, NSW 2006Australia
  2. 2.Cardiovascular Genetics Laboratory, Prince of Wales Hospital, Centre for Thrombosis and Vascular Research, University of New South Wales, SydneyAustralia
  3. 3.Department of Genetics, Southwest Foundation for Biomedical Research, 7620 loop 410, San Antonio, TX 78245-05310USA

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