Xenobiotic Metabolizing Enzyme Gene Polymorphisms Predict Response to Lung Volume Reduction Surgery

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Xenobiotic Metabolizing Enzyme Gene Polymorphisms Predict Response to Lung Volume Reduction Surgery

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dc.contributor.author Hersh, Craig Palmer
dc.contributor.author Demeo, Dawn Lisa
dc.contributor.author Reilly, John J.
dc.contributor.author Silverman, Edwin Kepner
dc.date.accessioned 2012-03-29T18:06:45Z
dc.date.issued 2007
dc.identifier.citation Hersh, Craig P., Dawn L. DeMeo, John J. Reilly, and Edwin K. Silverman. 2007. Xenobiotic metabolizing enzyme gene polymorphisms predict response to lung volume reduction surgery. Respiratory Research 8(1): 59. en_US
dc.identifier.issn 1465-9921 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:8462357
dc.description.abstract Background: In the National Emphysema Treatment Trial (NETT), marked variability in response to lung volume reduction surgery (LVRS) was observed. We sought to identify genetic differences which may explain some of this variability. Methods: In 203 subjects from the NETT Genetics Ancillary Study, four outcome measures were used to define response to LVRS at six months: modified BODE index, post-bronchodilator FEV1, maximum work achieved on a cardiopulmonary exercise test, and University of California, San Diego shortness of breath questionnaire. Sixty-four single nucleotide polymorphisms (SNPs) were genotyped in five genes previously shown to be associated with chronic obstructive pulmonary disease susceptibility, exercise capacity, or emphysema distribution. Results: A SNP upstream from glutathione S-transferase pi (GSTP1; p = 0.003) and a coding SNP in microsomal epoxide hydrolase (EPHX1; p = 0.02) were each associated with change in BODE score. These effects appeared to be strongest in patients in the non-upper lobe predominant, low exercise subgroup. A promoter SNP in EPHX1 was associated with change in BODE score (p = 0.008), with the strongest effects in patients with upper lobe predominant emphysema and low exercise capacity. One additional SNP in GSTP1 and three additional SNPs in EPHX1 were associated (p < 0.05) with additional LVRS outcomes. None of these SNP effects were seen in 166 patients randomized to medical therapy. Conclusion: Genetic variants in GSTP1 and EPHX1, two genes encoding xenobiotic metabolizing enzymes, were predictive of response to LVRS. These polymorphisms may identify patients most likely to benefit from LVRS. en_US
dc.language.iso en_US en_US
dc.publisher BioMed Central en_US
dc.relation.isversionof doi:10.1186/1465-9921-8-59 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2048957/pdf/ en_US
dash.license LAA
dc.title Xenobiotic Metabolizing Enzyme Gene Polymorphisms Predict Response to Lung Volume Reduction Surgery en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Respiratory Research en_US
dash.depositing.author Hersh, Craig Palmer
dc.date.available 2012-03-29T18:06:45Z
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US

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