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PLoS One DOI:10.1371/journal.pone.0085893

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

Publication TypeJournal Article
Year of Publication2014
AuthorsHamrefors, V, Hedblad, B, Hindy, G, J Smith, G, Almgren, P, Engström, G, Sjögren, M, Gränsbo, K, Orho-Melander, M, Melander, O
JournalPLoS One
Date Published2014
KeywordsAged, Cardiovascular Diseases, Chromosomes, Human, Pair 9, Educational Status, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Incidence, Male, Middle Aged, Polymorphism, Single Nucleotide, Proportional Hazards Models, Prospective Studies, Registries, Risk Factors, Smoking, Surveys and Questionnaires, Survival Rate, Sweden

AIMS: Genetic 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 RESULTS: A 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; P

CONCLUSION: Smoking 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.


Alternate JournalPLoS ONE
PubMed ID24465769
PubMed Central IDPMC3899088