TY - JOUR
T1 - Impact of inflammation, gene variants, and cigarette smoking on coronary artery disease risk
AU - Merhi, Mahmoud
AU - Demirdjian, Sally
AU - Hariri, Essa
AU - Sabbah, Nada
AU - Youhanna, Sonia
AU - Ghassibe-Sabbagh, Michella
AU - Naoum, Joseph
AU - Haber, Marc
AU - Othman, Raed
AU - Kibbani, Samer
AU - Chammas, Elie
AU - Kanbar, Roy
AU - Bayeh, Hamid el
AU - Chami, Youssef
AU - Abchee, Antoine
AU - Platt, Daniel E.
AU - Zalloua, Pierre
AU - Khazen, Georges
N1 - Publisher Copyright:
© 2015, Springer Basel.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
KW - CAD
KW - Inflammation
KW - Interaction
KW - Leukotriene
KW - Smoking-gene
UR - http://www.scopus.com/inward/record.url?scp=84937765279&partnerID=8YFLogxK
U2 - 10.1007/s00011-015-0821-1
DO - 10.1007/s00011-015-0821-1
M3 - Article
C2 - 25902778
AN - SCOPUS:84937765279
SN - 1023-3830
VL - 64
SP - 415
EP - 422
JO - Inflammation Research
JF - Inflammation Research
IS - 6
ER -
