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

作者：Merhi Mahmoud; Demirdjian Sally; Hariri Essa; Sabbah Nada; Youhanna Sonia; Ghassibe Sabbagh Michella; Naoum Joseph; Haber Marc; Othman Raed; Kibbani Samer; Chammas Elie; Kanbar Roy; el Bayeh Hamid; Chami Youssef; Abchee Antoine; Platt Daniel E; Zalloua Pierre^*; Khazen Georges

来源：Inflammation Research, 2015, 64(6): 415-422.

DOI：10.1007/s00011-015-0821-1

• CAD
• Inflammation
• Leukotriene
• Smoking-gene
• Interaction

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.

• 出版日期2015-6
• 单位IBM