PLoS ONE (Jan 2014)

Smoking modifies the associated increased risk of future cardiovascular disease by genetic variation on chromosome 9p21.

  • Viktor Hamrefors,
  • Bo Hedblad,
  • George Hindy,
  • J Gustav Smith,
  • Peter Almgren,
  • Gunnar Engström,
  • Marketa Sjögren,
  • Klas Gränsbo,
  • Marju Orho-Melander,
  • Olle Melander

DOI
https://doi.org/10.1371/journal.pone.0085893
Journal volume & issue
Vol. 9, no. 1
p. e85893

Abstract

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AimsGenetic predisposition for cardiovascular disease (CVD) is likely to be modified by environmental exposures. We tested if the associated risk of CVD and CVD-mortality by the single nucleotide polymorphism rs4977574 on chromosome 9p21 is modified by life-style factors.Methods and resultsA total of 24,944 middle-aged subjects (62% females) from the population-based Malmö-Diet-and-Cancer-Cohort were genotyped. Smoking, education and physical activity-levels were recorded. Subjects were followed for 15 years for incidence of coronary artery disease (CAD; N = 2309), ischemic stroke (N = 1253) and CVD-mortality (N = 1156). Multiplicative interactions between rs4977574 and life-style factors on endpoints were tested in Cox-regression-models. We observed an interaction between rs4977574 and smoking on incident CAD (P = 0.035) and CVD-mortality (P = 0.012). The hazard ratios (HR) per risk allele of rs4977574 were highest in never smokers (N = 9642) for CAD (HR = 1.26; 95% CI 1.13-1.40; PConclusionSmoking may modify the associated risk of CAD and CVD-mortality conferred by genetic variation on chromosome 9p21. Whether the observed attenuation of the genetic risk reflects a pathophysiological mechanism or is a result of smoking being such a strong risk-factor that it may eliminate the associated genetic effect, requires further investigation.