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

PLoS One. 2014 Aug 18;9(8):e104978. doi: 10.1371/journal.pone.0104978. eCollection 2014.

Abstract

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 PM10 (TPM10) 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 TPM10 and IL6 gene variants (rs1800795; rs2069827; rs2069840; rs10242595) on HRV indices and their interaction with average annual exposure to TPM10 were tested, applying a multivariable mixed linear model.

Results: No overall association of TPM10 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/m3 increment in yearly averaged TPM10 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; pinteraction(additive) = 0.028); and low frequency power (LF) (GG-carriers: -5.7%; 95%CI: -10.4 to -0.8; pinteraction(dominant) = 0.049).

Conclusions: Our results are consistent with the hypothesis that traffic-related air pollution decreases heart rate variability through inflammatory mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Autonomic Nervous System / drug effects
  • Autonomic Nervous System / metabolism
  • Cross-Sectional Studies
  • Electrocardiography
  • Female
  • Genotype
  • Heart Rate / drug effects
  • Humans
  • Interleukin-6 / genetics*
  • Male
  • Middle Aged
  • Particulate Matter / toxicity*
  • Polymorphism, Genetic / genetics*
  • Promoter Regions, Genetic / genetics*

Substances

  • Interleukin-6
  • Particulate Matter

Grants and funding

This work was supported by the Swiss National Science Foundation (grant numbers 33CSCO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, 4026-028099), the Federal Office for Forest, Environment and Landscape, the Federal Office of Public Health, the Federal Office of Roads and Transport, the canton's government of Aargau, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais and Zurich, the Swiss Lung League and the canton's Lung League of Basel Stadt/ Basel Landschaft, Geneva, Ticino, Valais and Zurich. No form of payment was given to any of the authors to produce the manuscript. The study received funding through peer-reviewed grants and donations from non-profit organizations as listed above. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.