Xenobiotic metabolizing enzyme gene polymorphisms predict response to lung volume reduction surgery
Year: 2007
Type: article
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.
Source: Respiratory Research
Institutions: Brigham and Women's Hospital, Harvard University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,490
Awards: G1207659464, G1439225947, G1605453878, Fine Mapping of a COPD Locus on Chromosome 19q, Pharmacogenetics of Asthma Treatment, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G278468722, CLINICAL COORDINATING CENTER FOR LVRS, G4153249725, Genetics of COPD in NETT, G4731985522, Fine Mapping of COPD Susceptibility Genes, G4899389735, G5181772611, G5332233980, G5484345081, CLINICAL CENTER FOR LVRS, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, Common Genetic Determinants of Asthma and COPD-PROGRAM PROJECT
OpenAlex ID: W2110624565