The role of inflammation in coronary artery disease (CAD) pathogenesis is well recognized. Moreover, smoking inhalation increases the activity of inflammatory mediators through an increase in leukotriene synthesis essential in atherosclerosis pathogenesis.
The aim of this study is to investigate the effect of “selected” genetic variants within the leukotriene (LT) pathway and other variants on the development of CAD.
CAD was detected by cardiac catheterization. Logistic regression was performed to investigate the association of smoking and selected susceptibility variants in the LT pathway including ALOX5AP, LTA4H, LTC4S, PON1, and LTA as well as CYP1A1 on CAD risk while controlling for age, gender, BMI, family history, diabetes, hyperlipidemia, and hypertension.
rs4769874 (ALOX5AP), rs854560 (PON1), and rs4646903 (CYP1A1 MspI polymorphism) are significantly associated with an increased risk of CAD with respective odds ratios of 1.53703, 1.67710, and 1.35520; the genetic variant rs9579646 (ALOX5AP) is significantly associated with a decreased risk of CAD (OR 0.76163). Moreover, a significant smoking-gene interaction is determined with CYP1A1 MspI polymorphism rs4646903 and is associated with a decreased risk of CAD in current smokers (OR 0.52137).
This study provides further evidence that genetic variation of the LT pathway, PON1, and CYP1A1 can modulate the atherogenic processes and eventually increase the risk of CAD in our study population. Moreover, it also shows the effect of smoking-gene interaction on CAD risk, where the CYP1A1 MspI polymorphism revealed a decreased risk in current smokers.
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Conflict of interest
The authors declare that they have no conflict of interest.
This study has been approved by the Lebanese American University Institutional Review Board and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. We would like to state that all the study participants gave their informed and written consent prior to their inclusion in the study.
Responsible Editor: John Di Battista.
M. Merhi, S. Demirdjian, E. Hariri and N. Sabbah contributed equaly.
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Merhi, M., Demirdjian, S., Hariri, E. et al. Impact of inflammation, gene variants, and cigarette smoking on coronary artery disease risk. Inflamm. Res. 64, 415–422 (2015). https://doi.org/10.1007/s00011-015-0821-1