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Impact of inflammation, gene variants, and cigarette smoking on coronary artery disease risk

  • Original Research Paper
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Abstract

Background

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.

Aim

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.

Methods

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.

Results

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).

Conclusion

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.

Ethical standards

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.

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Author notes

    Authors and Affiliations

    1. School of Medicine, Lebanese American University, P.O Box 36, Byblos, Lebanon

      Mahmoud Merhi, Essa Hariri, Nada Sabbah, Michella Ghassibe-Sabbagh, Joseph Naoum, Marc Haber, Elie Chammas, Roy Kanbar, Hamid el Bayeh, Youssef Chami & Pierre Zalloua

    2. School of Arts and Sciences, Brandeis University, Waltham, MA, USA

      Sally Demirdjian

    3. Division of Cardiology, Rafic Hariri University Hospital, Beirut, Lebanon

      Sonia Youhanna, Raed Othman & Samer Kibbani

    4. Department of Internal Medicine, American University of Beirut, Beirut, Lebanon

      Antoine Abchee

    5. Bioinformatics and Pattern Discovery, IBM T. J. Watson Research Centre, Yorktown Heights, NY, 10598, USA

      Daniel E. Platt

    6. Harvard School of Public Health, Boston, MA, 02215, USA

      Pierre Zalloua

    7. Department of Computer Science and Mathematics, School of Arts and Sciences, Lebanese American University, P.O Box 36, Byblos, Lebanon

      Georges Khazen

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    1. Mahmoud Merhi
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    Correspondence to Pierre Zalloua or Georges Khazen.

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    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

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    • DOI: https://doi.org/10.1007/s00011-015-0821-1

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