DNA variants, plasma levels and variability of Interleukin-6 in myocardial infarction survivors: Results from the AIRGENE study.

Introduction: Increased levels of interleukin 6 (IL-6), a marker for systemic inflammation, have been associated with cardiovascular morbidity and mortality. Materials and Methods: We investigated the influence of IL6 gene polymorphisms on mean level and variability of plasma IL-6 in a population of myocardial infarction survivors recruited in six European cities as part of the AIRGENE study. DNA from each individual was collected and genotyped for eight functional and tagging single nucleotide polymorphisms (SNPs) in the IL6 gene. Results: We analyzed 946 subjects with 5520 repeated plasma samples for IL-6 levels. For four IL6 SNPs in high linkage disequilibrium, heterozygous and homozygous minor allele genotypes were associated with an increase in mean plasma IL-6 levels. SNP rs1800795 was associated with a 6.3% increase in IL-6 (95% confidence interval [CI] 1.7-11.2%) For these SNPs, we found that genotypes associated with higher IL-6 levels also tended to be associated to higher between-individual variability of IL-6 levels on the log-scale than other genotypes. Variability over time within individuals varied little by genotype. Conclusions: We found four genetic polymorphisms in the IL6 gene associated with mean level and variability of plasma IL-6 between individuals in myocardial infarction survivors