Modifying Effect of a Common Polymorphism in the Interleukin-6 Promoter on the Relationship between Long-Term Exposure to Traffic-Related Particulate Matter and Heart Rate Variability

BACKGROUND: Exposure to particulate matter (PM) has been associated with an increase in many inflammatory markers, including interleukin 6 (IL6). Air pollution exposure has also been suggested to induce an imbalance in the autonomic nervous system (ANS), such as a decrease in heart rate variability (HRV). In this study we aimed to investigate the modifying effect of polymorphisms in a major proinflammatory marker gene, interleukin 6 (IL6), on the relationship between long-term exposure to traffic-related PM(10) (TPM(10)) and HRV. METHODS: For this cross-sectional study we analysed 1552 participants of the SAPALDIA cohort aged 50 years and older. Included were persons with valid genotype data, who underwent ambulatory 24-hr electrocardiogram monitoring, and reported on medical history and lifestyle. Main effects of annual average TPM(10) and IL6 gene variants (rs1800795; rs2069827; rs2069840; rs10242595) on HRV indices and their interaction with average annual exposure to TPM(10) were tested, applying a multivariable mixed linear model. RESULTS: No overall association of TPM(10) on HRV was found. Carriers of two proinflammatory G-alleles of the functional IL6 -174 G/C (rs1800795) polymorphism exhibited lower HRV. An inverse association between a 1 µg/m(3) increment in yearly averaged TPM(10) and HRV was restricted to GG genotypes at this locus with a standard deviation of normal-to-normal intervals (SDNN) (GG-carriers: −1.8%; 95% confidence interval −3.5 to 0.01; p(interaction(additive)) = 0.028); and low frequency power (LF) (GG-carriers: −5.7%; 95%CI: −10.4 to −0.8; p(interaction(dominant)) = 0.049). CONCLUSIONS: Our results are consistent with the hypothesis that traffic-related air pollution decreases heart rate variability through inflammatory mechanisms.