The influence of tumor necrosis factor -308 and C-reactive protein G1059C gene variants on serum concentration of C-reactive protein: evidence for an age-dependent association.

Background: C-reactive protein (CRP) synthesis and activity are modulated both by genetic and environmental factors. Data about the influence of genetic factors upon CRP concentration are sparse. We evaluated the hypothesis that allele variations in the genes encoding the CRP and TNF-alpha genes could modulate hs-CRP serum concentration in the general population.

Methods: Six hundred and eighty-four asymptomatic Brazilian individuals, selected between July 1998 and July 2001, 295 men (43.1%) and 389 women (56.9%) were studied. Laboratory assessment included: serum glucose, cholesterol, triglycerides, thyroid-stimulating hormone, uric acid and CRP measured by a high-sensitivity assay (hs-CRP). TNF -308 and CRP G1059C genotypes were obtained through PCR amplification and restriction enzyme digestion.

Results: Serum concentrations of hs-CRP were distributed into population quartiles. There was no significant difference of hs-CRP serum concentration regarding CRP gene G1059C polymorphism. However, there was a tendency for higher hs-CRP serum levels in individuals harboring the TNFA2 allele in quartile 4. In addition, ANOVA factorial modeling using log-transformed hs-CRP serum level as the dependent variable disclosed a significant association between hs-CRP and the TNFA2 allele following stratification for age quartiles (p=0.01). Finally, the presence of TNFA2 allele in this age group increased the odds of being in the fourth quartile of hs-CRP concentration (p<0.05, OR=5.1).

Conclusion: These findings suggest an association between a functional genetic variant of the TNF-alpha gene and hs-CRP levels at particular age groups.