Smoking modifies the associated increased risk of future cardiovascular disease by genetic variation on chromosome 9p21.
<h4>Aims</h4>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.<h4&...
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2014
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oai:doaj.org-article:1ec468902a3d4272b3e2a08a6d01bec32021-11-18T08:36:32ZSmoking modifies the associated increased risk of future cardiovascular disease by genetic variation on chromosome 9p21.1932-620310.1371/journal.pone.0085893https://doaj.org/article/1ec468902a3d4272b3e2a08a6d01bec32014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24465769/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Aims</h4>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.<h4>Methods and results</h4>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<0.001) and for CVD-mortality (HR = 1.40; 95% CI 1.20-1.63; P<0.001), whereas the risk increase by rs4977574 was attenuated in current smokers (N = 7000) for both CAD (HR = 1.05; 95%CI 0.95-1.16; P = 0.326) and CVD-mortality (HR = 1.08; 95%CI 0.94-1.23; P = 0.270). A meta-analysis supported the finding that the associated increased risk of CAD by the risk-allele was attenuated in smokers. Neither education nor physical activity-levels modified the associated risk of CAD, ischemic stroke and CVD mortality conferred by rs4977574.<h4>Conclusion</h4>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.Viktor HamreforsBo HedbladGeorge HindyJ Gustav SmithPeter AlmgrenGunnar EngströmMarketa SjögrenKlas GränsboMarju Orho-MelanderOlle MelanderPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e85893 (2014) |
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Medicine R Science Q |
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Medicine R Science Q Viktor Hamrefors Bo Hedblad George Hindy J Gustav Smith Peter Almgren Gunnar Engström Marketa Sjögren Klas Gränsbo Marju Orho-Melander Olle Melander Smoking modifies the associated increased risk of future cardiovascular disease by genetic variation on chromosome 9p21. |
| description |
<h4>Aims</h4>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.<h4>Methods and results</h4>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<0.001) and for CVD-mortality (HR = 1.40; 95% CI 1.20-1.63; P<0.001), whereas the risk increase by rs4977574 was attenuated in current smokers (N = 7000) for both CAD (HR = 1.05; 95%CI 0.95-1.16; P = 0.326) and CVD-mortality (HR = 1.08; 95%CI 0.94-1.23; P = 0.270). A meta-analysis supported the finding that the associated increased risk of CAD by the risk-allele was attenuated in smokers. Neither education nor physical activity-levels modified the associated risk of CAD, ischemic stroke and CVD mortality conferred by rs4977574.<h4>Conclusion</h4>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. |
| format |
article |
| author |
Viktor Hamrefors Bo Hedblad George Hindy J Gustav Smith Peter Almgren Gunnar Engström Marketa Sjögren Klas Gränsbo Marju Orho-Melander Olle Melander |
| author_facet |
Viktor Hamrefors Bo Hedblad George Hindy J Gustav Smith Peter Almgren Gunnar Engström Marketa Sjögren Klas Gränsbo Marju Orho-Melander Olle Melander |
| author_sort |
Viktor Hamrefors |
| title |
Smoking modifies the associated increased risk of future cardiovascular disease by genetic variation on chromosome 9p21. |
| title_short |
Smoking modifies the associated increased risk of future cardiovascular disease by genetic variation on chromosome 9p21. |
| title_full |
Smoking modifies the associated increased risk of future cardiovascular disease by genetic variation on chromosome 9p21. |
| title_fullStr |
Smoking modifies the associated increased risk of future cardiovascular disease by genetic variation on chromosome 9p21. |
| title_full_unstemmed |
Smoking modifies the associated increased risk of future cardiovascular disease by genetic variation on chromosome 9p21. |
| title_sort |
smoking modifies the associated increased risk of future cardiovascular disease by genetic variation on chromosome 9p21. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/1ec468902a3d4272b3e2a08a6d01bec3 |
| work_keys_str_mv |
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1718421547931140096 |