title: Impact of inflammation, gene variants, and cigarette smoking on coronary artery disease risk.
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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Medicine, Lebanese American University, P.O Box 36, Byblos, Lebanon.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Merhi
authors.forename: Sally
authors.initials: S
authors.lastname: Demirdjian
authors.forename: Essa
authors.initials: E
authors.lastname: Hariri
authors.forename: Nada
authors.initials: N
authors.lastname: Sabbah
authors.forename: Sonia
authors.initials: S
authors.lastname: Youhanna
authors.forename: Michella
authors.initials: M
authors.lastname: Ghassibe-Sabbagh
authors.forename: Joseph
authors.initials: J
authors.lastname: Naoum
authors.forename: Marc
authors.initials: M
authors.lastname: Haber
authors.forename: Raed
authors.initials: R
authors.lastname: Othman
authors.forename: Samer
authors.initials: S
authors.lastname: Kibbani
authors.forename: Elie
authors.initials: E
authors.lastname: Chammas
authors.forename: Roy
authors.initials: R
authors.lastname: Kanbar
authors.forename: Hamid El
authors.initials: HE
authors.lastname: Bayeh
authors.forename: Youssef
authors.initials: Y
authors.lastname: Chami
authors.forename: Antoine
authors.initials: A
authors.lastname: Abchee
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Platt
authors.forename: Pierre
authors.initials: P
authors.lastname: Zalloua
authors.forename: Georges
authors.initials: G
authors.lastname: Khazen
mesh_terms: D000368:Aged; D000483:Alleles; D043303:Aryldialkylphosphatase / Q000235:genetics; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics*; D003430:Cross-Sectional Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000235:genetics*; D015289:Leukotrienes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics*
chemical_list: D015289:Leukotrienes; D019363:Cytochrome P-450 CYP1A1; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human