Polymorphisms for microsomal epoxide hydrolase and genetic susceptibility to COPD

Park, Jong Y.; Chen, Lan; Wadhwa, Nina; Tockman, Melvyn S.

doi:10.3892/ijmm.15.3.443

Cited by 23 publications

(37 citation statements)

References 24 publications

(38 reference statements)

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“…They do not find any effect on the risk of COPD for either the T113C or the A139G polymorphisms. [13] HERSH [28] FU [27] BRØGGER [2] CHENG [26] PARK [25] ZIDZIK [24] VIBHUTI [23] MATHESON [22] KORYTINA [20] BUDHI [19] RODRIGUEZ [18] XIAO [17] TAKEYABU [16] YIM [15] PARK [14] SMITH [21] CHAPPELL [7] Overall . Meta-analysis of EPHX1 A139G genotype and risk of chronic obstructive pulmonary disease (COPD); overall and stratified analyses using both random and fixed effect models.…”

Section: Copdmentioning

confidence: 99%

“…[2,7,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]) investigating the EPHX1 T113C and A139G polymorphisms in relation to COPD or emphysema as the primary end-point were included. Two minor studies were excluded from the analyses, because we were unable to retrieve the original papers despite contacting the corresponding authors.…”

Section: Statistical Analysesmentioning

confidence: 99%

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EPHX1 polymorphisms, COPD and asthma in 47,000 individuals and in meta-analysis

Lee¹,

Nordestgaard²,

Dahl³

2010

European Respiratory Journal

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We tested the hypothesis that two well-characterised functional polymorphisms of the microsomal epoxide hydrolase gene (EPHX1), T113C and A139G, may influence susceptibility to chronic obstructive pulmonary disease (COPD) and asthma.We genotyped participants from the Copenhagen City Heart Study (n510,038) and the Copenhagen General Population Study (n537,022) for the T113C and A139G variants in the EPHX1 gene and measured lung function and recorded COPD hospitalisation and asthma and smoking history. Finally, we meta-analysed results from 19 studies including 7,489 COPD cases and 42,970 controls.The OR for spirometry-defined COPD or COPD hospitalisation did not differ from 1.0 for any of the EPHX1 genotypes or phenotypes overall, or in smokers or nonsmokers separately (p-value for trend 0.18-0.91). Likewise, EPHX1 genotypes or phenotypes did not associate with risk of asthma (p-value for trend 0.46-0.98). In meta-analysis, random effects OR for COPD in T113C heterozygotes and homozygotes versus non-carriers were 1.17 (0.99-1.38) and 1.38 (1.09-1.74), respectively. Corresponding values for A139G were 0.93 (0.83-1.05) and 0.89 (0.78-1.02).Our results indicate that genetically reduced microsomal epoxide hydrolase activity is not a major risk factor for COPD or asthma in the Danish population; however, meta-analysis cannot completely exclude a minor effect on COPD risk.

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Section: Copdmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

EPHX1 polymorphisms, COPD and asthma in 47,000 individuals and in meta-analysis

Lee¹,

Nordestgaard²,

Dahl³

2010

European Respiratory Journal

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“…In addition, a comparison of patients with severe COPD to those with mild-to-moderate disease revealed that the frequency of the homozygous His113His mEPHX exon 3 variant was significantly higher in severe COPD (Cheng et al 2004). In the study by Park et al (2005), a significantly increased risk for COPD was observed for subjects with the mEPHX (His113His) genotypes. On the other hand, two studies failed to demonstrate an association between low activity variant of mEPHX and COPD Zhang et al 2002).…”

Section: Microsomal Epoxide Hydrolasementioning

confidence: 99%

“…Most of the studies reported significant associations between low mEPHX activity genotypes and the risk for COPD Sandford et al 2001;Rodriguez et al 2002;Xiao et al 2003;Cheng et al 2004;Park et al 2005). In the study by Sandford et al (2001), a combination of a family history of COPD together with a homozygosity for the His 113 /His 139 haplotype in the mEPHX gene was associated with rapid decline of lung function.…”

Section: Microsomal Epoxide Hydrolasementioning

confidence: 99%

The role of gene polymorphisms in the pathogenesis of chronic obstructive pulmonary disease

et al. 2008

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Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Irreversible airflow limitation, both progressive and associated with an inflammatory response of the lungs to noxious particles or gases, is a hallmark of the disease. Cigarette smoking is the most important environmental risk factor for COPD, nevertheless, only approximately 20-30% of smokers develop symptomatic disease. Epidemiological studies, case-control studies in relatives of patients with COPD, and twin studies suggest that COPD is a genetically complex disease with environmental factors and many involved genes interacting together. Two major strategies have been employed to identify the genes and the polymorphisms that likely contribute to the development of complex diseases: association studies and linkage analyses. Biologically plausible pathogenetic mechanisms are prerequisites to focus the search for genes of known function in association studies. Protease-antiprotease imbalance, generation of oxidative stress, and chronic inflammation are recognized as the principal mechanisms leading to irreversible airflow obstruction and parenchymal destruction in the lung. Therefore, genes which have been implicated in the pathogenesis of COPD are involved in antiproteolysis, antioxidant barrier and metabolism of xenobiotic substances, inflammatory response to cigarette smoke, airway hyperresponsiveness, and pulmonary vascular remodelling. Significant associations with COPD-related phenotypes have been reported for polymorphisms in genes coding for matrix metalloproteinases, microsomal epoxide hydrolase, glutathione-S-transferases, heme oxygenase, tumor necrosis factor, interleukines 1, 8, and 13, vitamin D-binding protein and β-2-adrenergic receptor (ADRB2), whereas adequately powered replication studies failed to confirm most of the previously observed associations. Genome-wide linkage analyses provide us with a novel tool to identify the general locations of COPD susceptibility genes, and should be followed by association analyses of positional candidate genes from COPD pathophysiology, positional candidate genes selected from gene expression studies, or dense single nucleotide polymorphism panels across regions of linkage. Haplotype analyses of genes with multiple polymorphic sites in linkage disequilibrium, such as the ADRB2 gene, provide another promising field that has yet to be explored in patients with COPD. In the present article we review the current knowledge about gene polymorphisms that have been recently linked to the risk of developing COPD and/or may account for variations in the disease course.

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“…These studies included 9 Caucasian populations (Rodriguez et al, 2002;Korytina et al, 2003;Hersh et al, 2005;Park et al, 2005;Brøgger et al, 2006;Chappell et al, 2008;Židzik et al, 2008;Penyige et al, 2010;Lee et al, 2011) and 10 Eastern Asian populations (Takeyabu et al, 2000;Yim et al, 2000;Yoshikawa et al, 2000;Zhang et al, 2002;Budhi et al, 2003;Park et al, 2003;Cheng et al, 2004;Xiao et al, 2004;Fu et al, 2007;Hua et al, 2012) ( Table 1). The total number of samples in the Caucasian and Eastern Asian populations were 47,048 (6471 cases vs 40,577 controls) and 2586 (1228 cases vs 1358 controls), respectively.…”

Section: Literature Searchmentioning

confidence: 99%

Exploration of association between EPHX1 and chronic obstructive pulmonary disease on the basis of combined data mining

Liu¹,

Xia²,

Zhou³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Chronic obstructive pulmonary disease (COPD) is an important respiratory disease with high mortality. Although smoking is the major environmental risk factor for the development of COPD, only 10% of heavy smokers develop symptomatic disease, suggesting association between genetic susceptibilities and environmental influences. In recent years, as one of the most widely studied genes including tests for associations between a genetic variant and COPD, epoxide hydrolase 1 (EPHX1) was found to be involved in the metabolism of tobacco smoke, an important risk factor of COPD. However, genetic associations with COPD identified in studies on EPHX1 are controversial. To address this issue, except for performing the meta-analysis, which specially added our current study on two polymorphisms (T337C and A416G) of EPHX1, we performed combined data mining based on functional prediction algorithms of nonsynonymous single-nucleotide polymorphisms and gene-based variable threshold testing. Genetic variations in EPHX1 did not affect COPD in Caucasian and Eastern Asian population, which is supported by recent evidence. We found no association between EPHX1 and COPD; however, a minor effect of EPHX1 on COPD risk was not completely excluded; further replication studies with large samples are needed to confirm our findings.

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Polymorphisms for microsomal epoxide hydrolase and genetic susceptibility to COPD

Cited by 23 publications

References 24 publications

EPHX1 polymorphisms, COPD and asthma in 47,000 individuals and in meta-analysis

EPHX1 polymorphisms, COPD and asthma in 47,000 individuals and in meta-analysis

The role of gene polymorphisms in the pathogenesis of chronic obstructive pulmonary disease

Exploration of association between EPHX1 and chronic obstructive pulmonary disease on the basis of combined data mining

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