Genetic variations in detoxification enzymes and HIF‐1α in Japanese patients with COPD. (6th July 2011)

• Record Type: Journal Article
• Authors: Putra, Andika Chandra; Tanimoto, Keiji; Arifin, Marina; Antariksa, Budhi; Hiyama, Keiko
• Is Part Of: Clinical respiratory journal. Volume 7:Number 1(2013)
• Page Start: 7
• Page End: 15
• Publication Date: 2011-07-06
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiratory organs -- Periodicals; 616.24
• DOI: 10.1111/j.1752-699X.2011.00255.x
• Languages: English
• ISSNs: 1752-6981

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p> <bold>Introduction: </bold> Genetic factors contribute as major determinants in the pathophysiological mechanisms of chronic obstructive pulmonary disease (COPD). Therefore, identification of candidate genes and various gene polymorphisms have improved our understanding of COPD.</p> <p> <bold>Objectives: </bold> Clarify the genes, including <italic>HIF1A</italic>, that contribute to the development of COPD.</p> <p> <bold>Methods: </bold> We compared the genotype frequencies of 12 polymorphisms in seven detoxification‐related genes (<italic>GSTM1</italic>, <italic>GSTT1</italic>, <italic>GSTP1</italic> exon 5, <italic>CYP1A1</italic> exon 7, <italic>CYP1A1</italic> 3′‐flanking, <italic>CYP2E1</italic> intron 6, <italic>CYP2E1</italic> 5′‐flanking, <italic>EPHX1</italic> exon 3, <italic>EPHX1</italic> exon 4 and <italic>HMOX1</italic> promoter) and the hypoxia‐related <italic>HIF1A</italic> (<italic>C1772T</italic> and <italic>G1790A</italic>) genes between 48 Japanese patients with work‐related COPD who had a working history in a poison gas factory during World War II and two control groups (<italic>n</italic> = 172 and 110 subjects, respectively).</p> <p> <bold>Results: </bold> As expected, wild homozygotes for <italic>GSTP1</italic> Ile105Val and <italic>EPHX1</italic> slow/very slow phenotypes were associated with susceptibility (<italic>P</italic> = 0.031) and severity (<italic>P</italic> = 0.036) of COPD, respectively. Moreover, compound heterozygosity of transcription‐activating <italic>HIF1A</italic> polymorphisms was observed in two patients with COPD, but not in control individuals (<italic>P</italic> = 0.091).</p> <p> <bold>Conclusion: </bold> This is the first report that examined <italic>HIF1A</italic> polymorphisms in COPD and demonstrated a possible role of HIF‐1α in COPD, as well as <italic>GSTP1</italic> and <italic>EPHX1</italic>.</p> <p>Please cite this paper as: Putra AC, Tanimoto K, Arifin M, Antariksa B and Hiyama K. Genetic variations in detoxification enzymes and HIF‐1α in Japanese patients with COPD. <italic>Clin Respir J</italic> 2013; 7: 7–15.</p> </abstract>