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. 2010 Aug;7(4):262-8.
doi: 10.3109/15412555.2010.496821.

Polymorphisms in the superoxide dismutase-3 gene are associated with emphysema in COPD

I C Sørheim  1 , D L DeMeo, G Washko, A Litonjua, D Sparrow, R Bowler, P Bakke, S G Pillai, H O Coxson, D A Lomas, E K Silverman, C P Hersh; International COPD Genetics Network Investigators
Collaborators, Affiliations

Polymorphisms in the superoxide dismutase-3 gene are associated with emphysema in COPD

I C Sørheim et al. COPD. 2010 Aug.

Abstract

Superoxide dismutase-3 (SOD3) is a major extracellular antioxidant enzyme, and previous studies have indicated a possible role of this gene in chronic obstructive pulmonary disease (COPD). We hypothesized that polymorphisms in the SOD3 gene would be associated with COPD and COPD-related phenotypes. We genotyped three SOD3 polymorphisms (rs8192287 (E1), rs8192288 (I1), and rs1799895 (R213G)) in a case-control cohort, with severe COPD cases from the National Emphysema Treatment Trial (NETT, n = 389) and smoking controls from the Normative Aging Study (NAS, n = 472). We examined whether the single nucleotide polymorphisms (SNPs) were associated with COPD status, lung function variables, and quantitative computed tomography (CT) measurements of emphysema and airway wall thickness. Furthermore, we tried to replicate our initial findings in two family-based studies, the International COPD Genetics Network (ICGN, n = 3061) and the Boston Early-Onset COPD Study (EOCOPD, n = 949). In NETT COPD cases, the minor alleles of SNPs E1 and I1 were associated with a higher percentage of emphysema (%LAA950) on chest CT scan (p = .029 and p = .0058). The association with E1 was replicated in the ICGN family study, where the minor allele was associated with more emphysema (p = .048). Airway wall thickness was positively associated with the E1 SNP in ICGN; however, this finding was not confirmed in NETT. Quantitative CT data were not available in EOCOPD. The SNPs were not associated with lung function variables or COPD status in any of the populations. In conclusion, polymorphisms in the SOD3 gene were associated with CT emphysema but not COPD susceptibility, highlighting the importance of phenotype definition in COPD genetics studies.

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Conflict of interest statement

DECLARATION OF INTEREST:

ICS received lecture fees from AstraZeneca in 2008, and lecture fees and a travel grant from GlaxoSmithKline in 2009. DLD has no conflicts of interest to disclose. GW has no conflicts of interest to disclose. AL has no conflicts of interest to disclose. DS has no conflicts of interest to disclose. RB has no conflicts of interest to disclose. PB has received speaking fees from GSK and AstraZeneca, and is a principle investigator in a GSK sponsored study. SGP holds stocks in GlaxoSmithKline and is an employee of Roche Pharmaceuticals. HOC has served on an advisory board for GSK in 2006–2009. In addition HOC is the co-investigator on two multi-center studies sponsored by GSK and has received travel expenses to attend meetings related to the project. HOC has three contract service agreements with GSK to quantify the CT scans in subjects with COPD and a service agreement with Spiration Inc to measure changes in lung volume in subjects with severe emphysema. HOC is the co-investigator (D Sin PI) on a Canadian Institutes of Health – Industry (Wyeth) partnership grant. There is no financial relationship between any industry and the current study. DAL receives grant support and lecture and consultancy fees from GlaxoSmithKline. EKS received an honorarium for a talk on COPD genetics in 2006, grant support for two studies of COPD genetics, and consulting fees from GlaxoSmithKline. He also received honoraria in 2007 and 2008 and consulting fees from AstraZeneca. CPH has no conflicts of interest to disclose.

Comment in

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