Genetic Determinants of Emphysema Distribution in the National Emphysema Treatment Trial

Dawn L DeMeo; Craig P Hersh; Eric A Hoffman; Augusto A Litonjua; Ross Lazarus; David Sparrow; Joshua O Benditt; Gerard Criner; Barry Make; Fernando J Martinez; Paul D Scanlon; Frank C Sciurba; James P Utz; John J Reilly; Edwin K Silverman

doi:10.1164/rccm.200612-1797OC

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Genetic Determinants of Emphysema Distribution in the National Emphysema Treatment Trial

Journal article

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Genetic Determinants of Emphysema Distribution in the National Emphysema Treatment Trial

Dawn L DeMeo, Craig P Hersh, Eric A Hoffman, Augusto A Litonjua, Ross Lazarus, David Sparrow, Joshua O Benditt, Gerard Criner, Barry Make, Fernando J Martinez, …

American journal of respiratory and critical care medicine, Vol.176(1), pp.42-48

07/01/2007

DOI: 10.1164/rccm.200612-1797OC

PMCID: PMC2049064

PMID: 17363767

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Abstract

Rationale : Computed tomography (CT) scanning of the lung may reduce phenotypic heterogeneity in defining subjects with chronic obstructive pulmonary disease (COPD), and allow identification of genetic determinants of emphysema severity and distribution. Objectives : We sought to identify genes associated with CT scan distribution of emphysema in individuals without α 1 -antitrypsin deficiency but with severe COPD. Methods : We evaluated baseline CT densitometry phenotypes in 282 individuals with emphysema enrolled in the Genetics Ancillary Study of the National Emphysema Treatment Trial, and used regression models to identify genetic variants associated with emphysema distribution. Measurements and Main Results : Emphysema distribution was assessed by two methods—assessment by radiologists and by computerized density mask quantitation, using a threshold of −950 Hounsfield units. A total of 77 polymorphisms in 20 candidate genes were analyzed for association with distribution of emphysema. GSTP1 , EPHX1 , and MMP1 polymorphisms were associated with the densitometric, apical-predominant distribution of emphysema (p value range = 0.001–0.050). When an apical-predominant phenotype was defined by the radiologist scoring method, GSTP1 and EPHX1 single-nucleotide polymorphisms were found to be significantly associated. In a case–control analysis of COPD susceptibility limited to cases with densitometric upper-lobe–predominant cases, the EPHX1 His139Arg single-nucleotide polymorphism was associated with COPD (p = 0.005). Conclusions : Apical and basal emphysematous destruction appears to be influenced by different genes. Polymorphisms in the xenobiotic enzymes, GSTP1 and EPHX1 , are associated with apical-predominant emphysema. Altered detoxification of cigarette smoke metabolites may contribute to emphysema distribution, and these findings may lead to further insight into genetic determinants of emphysema.

computed tomography

genetics

C. Chronic Obstructive Pulmonary Disease

association analysis

COPD

emphysema

Details

Title: Subtitle: Genetic Determinants of Emphysema Distribution in the National Emphysema Treatment Trial
Creators: Dawn L DeMeo - Channing Laboratory and
Craig P Hersh - Channing Laboratory and
Eric A Hoffman - Channing Laboratory and
Augusto A Litonjua - Channing Laboratory and
Ross Lazarus - Channing Laboratory and
David Sparrow - Channing Laboratory and
Joshua O Benditt - Channing Laboratory and
Gerard Criner - Channing Laboratory and
Barry Make - Channing Laboratory and
Fernando J Martinez - Channing Laboratory and
Paul D Scanlon - Channing Laboratory and
Frank C Sciurba - Channing Laboratory and
James P Utz - Channing Laboratory and
John J Reilly - Channing Laboratory and
Edwin K Silverman - Channing Laboratory and
Resource Type: Journal article
Publication Details: American journal of respiratory and critical care medicine, Vol.176(1), pp.42-48
DOI: 10.1164/rccm.200612-1797OC
PMID: 17363767
PMCID: PMC2049064
NLM abbreviation: Am J Respir Crit Care Med
ISSN: 1073-449X
eISSN: 1535-4970
Publisher: American Thoracic Society
Language: English
Date published: 07/01/2007
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
Record Identifier: 9984051887802771

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