Synergistic effect of cytochrome P450 epoxygenase CYP2J2*7 polymorphism with smoking on the onset of premature myocardial infarction

Ping Yen Liu, Yi Heng Li, Ting Hsing Chao, Hua Lin Wu, Li Jen Lin, Liang Miin Tsai, Jyh Hong Chen

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Abstract

Objectives: 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). Patients/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.

Original languageEnglish
Pages (from-to)199-206
Number of pages8
JournalAtherosclerosis
Volume195
Issue number1
DOIs
Publication statusPublished - 2007 Nov 1

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All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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