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Superoxide dismutase 3 polymorphism associated with reduced lung function in two large populations.
Morten Dahl1, Russell P Bowler, Klaus Juul
1Department of Clinical Biochemistry and Copenhagen General Population Study, Herlev Hospital and Copenhagen University Hospital, Copenhagen, Denmark.
Novel superoxide dismutase 3 (SOD3) gene variants are linked to reduced lung function. Homozygosity for these SOD3 polymorphisms may increase the risk of chronic obstructive pulmonary disease (COPD).
Area of Science:
- Genetics and Pulmonary Medicine
- Molecular Biology and Respiratory Health
Background:
- Superoxide dismutase 3 (SOD3) plays a role in preventing oxidative damage to lung matrix components.
- Alterations in SOD3 expression or function may impact lung matrix homeostasis and overall pulmonary function.
Purpose of the Study:
- To discover novel SOD3 gene polymorphisms associated with lung function.
- To investigate the link between SOD3 polymorphisms and chronic obstructive pulmonary disease (COPD).
Main Methods:
- Resequencing identified two novel SOD3 polymorphisms (E1 and I1).
- Genotyping of over 9,000 individuals from the Copenhagen City Heart Study.
- Validation in a cross-sectional analysis of over 35,000 individuals from the Copenhagen General Population Study.
Main Results:
- Homozygotes for the novel E1/I1 SOD3 polymorphisms showed significantly reduced forced vital capacity (FVC) % predicted.
- These findings were confirmed in two large, independent population studies.
- E1/I1 homozygotes exhibited increased hazard ratios for COPD hospitalization and mortality.
Conclusions:
- Two novel SOD3 polymorphisms were identified in a conserved gene region.
- Individuals homozygous for these polymorphisms demonstrate reduced lung function (FVC % predicted).
- The E1/I1 genotype is associated with reduced lung function and potentially increased COPD risk.
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