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

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.