The TNF-alpha G-308A polymorphism is associated with C-reactive protein levels: the HERITAGE Family Study

Vascul Pharmacol. 2006 May;44(5):377-83. doi: 10.1016/j.vph.2006.02.002. Epub 2006 Mar 3.


Objective: Pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), stimulate the release of C-reactive protein (CRP). We investigated the association between the TNF-alpha G-308A polymorphism and plasma CRP levels.

Methods: Subjects were 456 White (225 men, 231 women) and 232 Black (83 men, 149 women) healthy adults who underwent a 20-week standardized exercise program in the HERITAGE Family Study. The TNF-alpha gene promoter polymorphism was determined using PCR amplification followed by NcoI digestion. Plasma CRP was measured using a high-sensitivity assay.

Results: Genotype frequencies were in Hardy-Weinberg equilibrium. After adjustment for age, smoking, alcohol consumption, maximal oxygen uptake and, in women, hormone use, the AA homozygotes for the G-308A polymorphism had higher baseline CRP levels than other genotypes in White and Black men (P<0.001 and P = 0.044, respectively) and in Black women (P = 0.032). Body mass index partly explained these associations in Blacks. The exercise program results provided further evidence for an association with the polymorphism. Among those with high CRP at baseline (> or = 3.0 mg/L), regular exercise decreased CRP less in AA homozygotes than in other genotypes (P = 0.043).

Conclusion: The AA genotype of the TNF-alpha G-308A polymorphism is associated with higher plasma CRP levels and less favorable CRP response to regular exercise.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • African Continental Ancestry Group / genetics
  • Aged
  • C-Reactive Protein / metabolism*
  • European Continental Ancestry Group / genetics
  • Exercise / physiology*
  • Family
  • Female
  • Gene Frequency
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Physical Education and Training
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics*
  • Sex Factors
  • Tumor Necrosis Factor-alpha / genetics*


  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein