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

Hanna Maaria Lakka, Timo A. Lakka, Tuomo Rankinen, Treva Rice, D. C. Rao, Arthur S. Leon, James S. Skinner, Claude Bouchard

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Objective: Pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), stimulate the release of C-reactive protein (CRP). We investigated the association between the TNF-α 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-α 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 (≥ 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-α G-308A polymorphism is associated with higher plasma CRP levels and less favorable CRP response to regular exercise.

Original languageEnglish (US)
Pages (from-to)377-383
Number of pages7
JournalVascular Pharmacology
Issue number5
StatePublished - May 2006

Bibliographical note

Funding Information:
The HERITAGE Family Study is supported by the NHLBI through Grants HL45670 (to C.B.), HL47323 (to Dr. Leon), HL47317 (to Dr. Rao), HL47327 (to Dr Skinner), and HL47321 (to Dr. Wilmore). Dr. H.-M. Lakka was supported by grants from University of Kuopio, Finnish Medical Foundation, Maud Kuistila Memorial Foundation and Finnish Cultural Foundation. Dr. Leon is partially supported by the Henry L. Taylor endowed Professorship in Exercise Science and Health Enhancement. Dr. Bouchard is partially supported by the George A. Bray Chair in Nutrition.


  • Adiposity
  • C-reactive protein
  • Inflammation
  • Polymorphism
  • Tumor necrosis factor alpha

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