Interaction between air pollution exposure and genes in relation to levels of inflammatory markers and risk of myocardial infarction

OBJECTIVES: Air pollution exposure induces cardiovascular effects, possibly via systemic inflammation and coagulation misbalance. Genetic variation may determine individual susceptibility. Our aim was to investigate effect modification by inflammation (Interleukin6 (IL6), tumour necrosis factor-α (TNF-α)) and coagulation (fibrinogen Bβ, plasminogen activator inhibitor-1 (PAI-1)) gene variants on the effect of long-term or short-term air pollution exposure on both blood marker levels and non-fatal myocardial infarction (MI) risk. DESIGN: Population-based case-control study with a nested case-crossover study. Gene-environment interactions for short-term and long-term air pollution on blood marker levels were studied in population controls, for long-term exposure on MI risk using case-control design, and for short-term exposure on MI onset using case-crossover design. SETTING: The Stockholm Heart Epidemiology Programme (SHEEP) conducted in 1992-1994 in Stockholm, Sweden. Spatial modelling was used to assess long-term (up to 30 years retrospectively) air pollution exposure to traffic-NO2 and heating-SO2 emissions at home addresses. Urban background NO2, SO2, PM10 and O3 measurements were used to estimate short-term (up to 5 days) air pollution exposure. PARTICIPANTS: 1192 MI cases and 1506 population controls aged 45-70 years. OUTCOMES: The levels of blood markers of inflammation (IL-6, TNF-α) and coagulation (fibrinogen, PAI-1) and MI risk. RESULTS: We observed gene-environment interaction for several IL6 and TNF SNPs in relation to inflammation blood marker levels. One-year traffic-NO2 exposure was associated with higher IL-6 levels with each additional IL6-174C allele, and 1-year heating-SO2 exposure with higher levels of TNF-α in TNF-308AA homozygotes versus -308G carriers. Short-term air pollution exposure also interacted with IL6 and TNF in relation to marker levels. The risk of MI followed the effect on blood markers in each genotype group. CONCLUSIONS: Genetic variants in IL6 and TNF may modify effects of long-term and short-term air pollution exposure on inflammatory marker levels and MI risk.