TY - JOUR
T1 - Microsomal epoxide hydrolase genotype and risk of myocardial infarction
AU - Cornelis, Marilyn C.
AU - El-Sohemy, Ahmed
AU - Campos, Hannia
N1 - Funding Information:
Acknowledgments This research was supported by grants from the Canadian Institutes of Health Research (No. MOP-53147), and the National Institutes of Health (No. HL 60692 and HL 071888). M. C. Cornelis is a recipient of a Natural Sciences and Engineering Research Council of Canada postgraduate scholarship. A. El-Sohemy holds a Canada Research Chair in Nutrigenomics. We thank Xinia Siles, RD, project director at the Centroamericano de Poblacion, Universidad de Costa Rica, for directing all the data collection, and Ana Baylin, MD, DrPh, Department of Nutrition, Harvard University of Public Health, for data monitoring and management throughout the study.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/9
Y1 - 2007/9
N2 - DNA damage caused by mutagens found in tobacco smoke may contribute to the development of coronary heart disease (CHD). Microsomal epoxide hydrolase (EPHX1) is involved in the metabolism of tobacco smoke mutagens and an amino acid substitution (H139R) in exon 4 of the EPHX1 gene is associated with increased enzyme activity. The objective of this study was to investigate the effect of EPHX1 genotype on risk of myocardial infarction (MI) and to determine whether smoking interacts with genotype to modify risk. Cases (n = 2,022) with a first acute non-fatal MI and population-based controls (n = 2,022) living in Costa Rica, matched for age, sex and area of residence were genotyped by RFLP-PCR. Smoking status was determined by questionnaire. The frequency of the R139 allele was 17% for both cases and controls. EPHX1 genotype was not associated with risk of MI, regardless of smoking status. Compared to individuals with the HH genotype, the multivariate adjusted odds ratio (95% confidence interval) for risk of MI was 0.95 (0.81-1.11) for individuals with the HR genotype and 1.18 (0.79-1.76) for those with the RR genotype. These results suggest that EPHX1 does not play a significant role in the development of CHD.
AB - DNA damage caused by mutagens found in tobacco smoke may contribute to the development of coronary heart disease (CHD). Microsomal epoxide hydrolase (EPHX1) is involved in the metabolism of tobacco smoke mutagens and an amino acid substitution (H139R) in exon 4 of the EPHX1 gene is associated with increased enzyme activity. The objective of this study was to investigate the effect of EPHX1 genotype on risk of myocardial infarction (MI) and to determine whether smoking interacts with genotype to modify risk. Cases (n = 2,022) with a first acute non-fatal MI and population-based controls (n = 2,022) living in Costa Rica, matched for age, sex and area of residence were genotyped by RFLP-PCR. Smoking status was determined by questionnaire. The frequency of the R139 allele was 17% for both cases and controls. EPHX1 genotype was not associated with risk of MI, regardless of smoking status. Compared to individuals with the HH genotype, the multivariate adjusted odds ratio (95% confidence interval) for risk of MI was 0.95 (0.81-1.11) for individuals with the HR genotype and 1.18 (0.79-1.76) for those with the RR genotype. These results suggest that EPHX1 does not play a significant role in the development of CHD.
KW - DNA damage
KW - Genotype
KW - Microsomal epoxide hydrolase
KW - Myocardial infarction
KW - Smoking
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U2 - 10.1007/s00204-007-0198-1
DO - 10.1007/s00204-007-0198-1
M3 - Article
C2 - 17380322
AN - SCOPUS:34547793694
SN - 0003-9446
VL - 81
SP - 641
EP - 645
JO - Archiv fur Toxikologie
JF - Archiv fur Toxikologie
IS - 9
ER -