Abstract
Inflammation is known to be a major component of atherosclerosis, and cigarette smoking is known to induce a systemic inflammatory response. We therefore, investigated possible gene–environment interactions between various inflammation-related gene polymorphisms and cigarette smoking on the risk of myocardial infarction (MI) in the Physician’s Health Study (PHS), a cohort of initially healthy middle-aged men. We used a nested case-control design consisting of 522 MI cases and 2,089 controls derived from PHS. Eleven inflammatory polymorphisms were studied using logistic regression analysis: eotaxin (ala23thr), intercellular adhesion molecule 1 (gly241arg), interleukin-4 (582C>T), interleukin-4 receptor (ile75val, gln576arg), interleukin-6 (−174G>C), interleukin-10 (−571C>A), P-selectin (val640leu, thr756pro, ser330asn), and vascular cell adhesion molecule 1 (−1594T>C). Interactions of smoking with all the three modes of inheritance (additive, dominant, recessive) were tested. Statistically significant (P<0.05) interaction terms were found for interleukin-4 receptor (ile75val), with odds ratios of 0.52 (95%CI:0.29–0.95) for Ile–Val and 0.34 (95%CI:0.14–0.83) for Val-Val, compared to the wildtype Ile-Ile; for interleukin-6 (−174G>C) with odds ratios of 2.16 (1.14–4.09) for GC and 0.81 (0.31–2.12) for CC, compared to the wildtype GG; and for P-selectin (ser330asn) with odds ratios of 0.48 (0.24–0.95) for Ser-Asn and 1.08 (0.29–3.93) for Asn-Asn, compared to the wildtype Ser-Ser, with these effects occurring only among the smokers. These data raise the possibility of interaction between the smoking status and certain inflammatory polymorphisms on the risk of MI in men. However, these results should be interpreted with caution due to the potential for false positive results that can arise from analyses with multiple comparisons.
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Funding for this project was obtained from the Donald W. Reynolds Foundation, Las Vegas, NV, USA.
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Rosner, S.A., Ridker, P.M., Zee, R.Y.L. et al. Interaction between inflammation-related gene polymorphisms and cigarette smoking on the risk of myocardial infarction in the Physician’s Health Study. Hum Genet 118, 287–294 (2005). https://doi.org/10.1007/s00439-005-0052-6
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DOI: https://doi.org/10.1007/s00439-005-0052-6