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

  • Ping-Yen Liu
    Affiliations
    Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Medical Center, Tainan, Taiwan

    Cardiovascular Research Center, National Cheng Kung University, Tainan, Taiwan
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  • Yi-Heng Li
    Affiliations
    Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Medical Center, Tainan, Taiwan

    Cardiovascular Research Center, National Cheng Kung University, Tainan, Taiwan
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  • Ting-Hsing Chao
    Affiliations
    Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Medical Center, Tainan, Taiwan

    Cardiovascular Research Center, National Cheng Kung University, Tainan, Taiwan
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  • Hua-Lin Wu
    Affiliations
    Cardiovascular Research Center, National Cheng Kung University, Tainan, Taiwan

    Department of Biochemistry and Molecular Biology, School of Medicine, National Cheng Kung University, Tainan, Taiwan
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  • Li-Jen Lin
    Affiliations
    Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Medical Center, Tainan, Taiwan

    Cardiovascular Research Center, National Cheng Kung University, Tainan, Taiwan
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  • Liang-Miin Tsai
    Affiliations
    Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Medical Center, Tainan, Taiwan

    Cardiovascular Research Center, National Cheng Kung University, Tainan, Taiwan
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  • Jyh-Hong Chen
    Correspondence
    Corresponding author at: Division of Cardiology, Department of Internal Medicine, School of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan. Tel.: +886 6 235 3535x2389; fax: +886 6 275 3834.
    Affiliations
    Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Medical Center, Tainan, Taiwan

    Cardiovascular Research Center, National Cheng Kung University, Tainan, Taiwan
    Search for articles by this author

      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.

      Keywords

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