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

Research output: Contribution to journalArticle

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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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Cytochrome P-450 Enzyme System
Smoking
Myocardial Infarction
Alleles
Confidence Intervals
Vascular Endothelium
Vasodilator Agents
Nicotine
DNA Sequence Analysis
Arachidonic Acid
Blood Vessels
arachidonate epoxygenase
Diabetes Mellitus
Logistic Models
Genotype
Regression Analysis
Hypertension
Inflammation
Polymerase Chain Reaction
Acids

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

@article{47645e249caa440bb3e80bb3e1a8d21e,
title = "Synergistic effect of cytochrome P450 epoxygenase CYP2J2*7 polymorphism with smoking on the onset of premature myocardial infarction",
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.",
author = "Ping-Yen Liu and Yi-Heng Li and Ting-Hsing Chao and Hua-Lin Wu and Lin, {Li Jen} and Liang-Miin Tsai and Chen, {Jyh Hong}",
year = "2007",
month = "11",
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language = "English",
volume = "195",
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Synergistic effect of cytochrome P450 epoxygenase CYP2J2*7 polymorphism with smoking on the onset of premature myocardial infarction. / Liu, Ping-Yen; Li, Yi-Heng; Chao, Ting-Hsing; Wu, Hua-Lin; Lin, Li Jen; Tsai, Liang-Miin; Chen, Jyh Hong.

In: Atherosclerosis, Vol. 195, No. 1, 01.11.2007, p. 199-206.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synergistic effect of cytochrome P450 epoxygenase CYP2J2*7 polymorphism with smoking on the onset of premature myocardial infarction

AU - Liu, Ping-Yen

AU - Li, Yi-Heng

AU - Chao, Ting-Hsing

AU - Wu, Hua-Lin

AU - Lin, Li Jen

AU - Tsai, Liang-Miin

AU - Chen, Jyh Hong

PY - 2007/11/1

Y1 - 2007/11/1

N2 - 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.

AB - 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.

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