Association between TNF and IL-1 bloc polymorphisms and plasma MCP-1 concentration

Background: Circulating MCP-1 concentration was found to be increased in cardiovascular diseases and is of high interest in the list of biomarkers of atherosclerosis. TNF-alpha, LT-alpha, IL-1 alpha and 1L-1 beta are four proinflammatory cytokines that regulate MCP-1 concentration in vitro. We hypothesized that specific genetic polymorphisms in TNF, LTA, IL-1A and IL-1B genes could modulate plasma MCP-1 concentration. Methods: Plasma MCP-1 concentration was quantified with a biochip array analyzer in 395 adults from the Stanislas family study. TNF -308G > A, LTA 252A > G (A=TNFB2, G=TNFB1), IL-1A-889C > T and IL-lB 3954C > T were genotyped with a prototypic multilocus genotyping assay. Results: Among the four polymorphisms studied only LTA 252A > G and TNF -308G > A were significantly associated with plasma MCPA concentration (p = 0.005 and p = 0.038, respectively) after adjustment for covariates (age, sex, smoking, monocyte count and hematocrit). Carriers of the 252A allele or the -308G had lower MCP-1 concentrations than carriers of the 252G or the -308A alleles, respectively. Moreover, as TNF and LTA genes were in linkage disequilibrium, the TNF bloc haplotypes were compared with respect to MCP-1 concentration, and a significant association (p = 0.021) was observed, due only to the LTA polymorphism. This association remained significant even after adjustment for TNF-alpha and hs-CRP concentrations. Conclusion: A functional polymorphism within the TNF bloc could modulate MCP-1 concentration and seems more likely to be near to the LTA 252A > G polymorphism than to the TNF -308G > A one. In addition, the association found in healthy French adults is independent of other actors of inflammation such as TNF-a and hs-CRP. (c) 2006 Elsevier Ireland Ltd. All rights reserved.