Synergistic effect of cytochrome P450 epoxygenase CYP2J2*7 polymorphism with smoking on the onset of premature myocardial infarction.
OBJECTIVE
Cytochrome P450 (CYP) 2J2 is expressed in vascular endothelium and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs), which are potent endogenous vasodilators and inhibitors of vascular inflammation. We aimed to elucidate the relationship between the functional CYP2J2*7 polymorphism and smoking for the onset of premature myocardial infarction (MI).


METHODS
We studied 200 patients with acute MI onset under 45 years (84% men) and 200 sex- and age-matched controls. The polymorphism was determined using PCR and direct DNA sequencing analysis.


RESULTS
The CYP2J2*7 GT+TT genotype was significantly more prevalent in premature MI patients (32.0% versus 22.0%; p=0.02). Multiple logistic regression analysis showed four independent risk factors: the CYP2J2*7 T allele (OR 1.78, 95% confidence interval [CI] 1.1-6.4; p=0.02), smoking (OR 3.05, 95% CI 1.6-7.3; p<0.01), diabetes mellitus (OR 3.24, 95% CI 1.2-6.6; p<0.01), and hypertension (OR 1.95, 95% CI 1.1-5.7; p<0.01). Among non-smoking patients, the CYP2J2*7 T allele was associated with a 1.3-fold risk. However, smoking T-allele carriers had a significantly 6.7-fold higher risk (p=0.01 for interaction). This variant, but not wild type, significantly reduced promoter activity with nicotine in vitro. EET metabolites were significantly lower among CYP2J2*7 T allele carriers than the GG subjects (p<0.05). Smoking could further lower EET concentrations in T allele carriers than the non-smokers, especially in MI patients (3.3+/-1.0 ng/mL versus 6.8+/-1.3 ng/mL; p=0.001).


CONCLUSIONS
The CYP2J2*7 polymorphism and premature MI were synergistically and significantly associated in Taiwanese patients.
Liu
Ping-Yen
PY
Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Medical Center, Tainan, Taiwan.
Li
Yi-Heng
YH
Chao
Ting-Hsing
TH
Wu
Hua-Lin
HL
Lin
Li-Jen
LJ
Tsai
Liang-Miin
LM
Chen
Jyh-Hong
JH
D000328:Adult; D017668:Age of Onset; D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism; D016022:Case-Control Studies; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism; D010105:Oxygenases / Q000235:genetics* / Q000502:physiology*; D011110:Polymorphism, Genetic; D012737:Sex Factors
D001095:Arachidonic Acids; C000717350:CYP2J2 protein, human; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D000090762:Cytochrome P-450 CYP2J2