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Microsomal epoxide hydrolase genotypes and chronic obstructive pulmonary disease in Japanese.

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Polymorphisms in the gene for microsomal epoxide hydrolase (mEPHX), an enzyme involved in the protective mechanism against oxidative stress, have been reported to be associated with individual susceptibility to the development of chronic obstructive pulmonary disease (COPD). The polymorphisms in exons 3 and 4 in the mEPHX gene were examined in a total of 358 Japanese individuals, including 40 patients with COPD and 71 patients with lung cancer. The overall frequencies of variant allele for mEPHX codons 113 (exon 3) and 139 (exon 4) were 44% and 14%, respectively. Moreover, a novel single nucleotide polymorphism (estimated allele frequency: 0.29) was identified in Japanese at 20 bp downstream of the codon 113 polymorphism with strong linkage disequilibrium with the wild allele for codon 113. While the frequencies of variant allele and proportions of individuals homozygous variant for codon 113, assumed having very slow mEPHX activity, were similar among COPD or lung cancer patients and the control population, they were significantly higher in patients with severe COPD than in those with mild COPD [P=0.0225, odds ratio 2.9 (95%CI 1.1-7.4); P=0.0350, respectively]. Thus, we found that the frequency of the variant allele for mEPHX codon 113 is higher in Japanese than that in Caucasians (P=0.0028), a novel silent polymorphism exists in exon 3 and shows strong linkage disequilibrium with the wild allele for codon 113, and individual homozygous variants for codon 113 may be associated with development of advanced COPD rather than the susceptibility to COPD.
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Document Type: Research Article

Affiliations: Second Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan.

Publication date: January 1, 2000

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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