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A disintegrin and metalloprotease 33 polymorphisms and lung function decline in the general population
Cleo C van Diemen1, Dirkje S Postma, Judith M Vonk
1Department of Epidemiology and Bioinformatics, University of Groningen, The Netherlands.
Summary
Single nucleotide polymorphisms (SNPs) in the ADAM33 gene are linked to faster lung function decline in the general population. Specific ADAM33 SNPs also increase the risk for developing chronic obstructive pulmonary disease (COPD).
Area of Science:
- Genetics
- Pulmonology
- Epidemiology
Background:
- A disintegrin and metalloprotease 33 (ADAM33) is a known susceptibility gene for asthma.
- Specific single nucleotide polymorphisms (SNPs) in ADAM33 correlate with accelerated lung function decline in asthma patients.
Purpose of the Study:
- To investigate the association between ADAM33 SNPs and accelerated lung function loss in the general population.
- To determine if ADAM33 SNPs are risk factors for chronic obstructive pulmonary disease (COPD).
Main Methods:
- Genotyping of 1,390 subjects from the Vlagtwedde-Vlaardingen cohort for eight ADAM33 SNPs.
- Longitudinal analysis of lung function (FEV1) decline over 25 years using linear mixed effects models.
- COPD defined as GOLD stage 2 or higher; SNP prevalence analyzed using chi(2) tests.
Main Results:
- Accelerated FEV1 decline (4.9-9.6 ml/year) was observed in individuals with specific homozygous or heterozygous ADAM33 SNP genotypes.
- Prevalence of SNPs F+1, S_1, S_2, and T_2 was significantly higher in subjects diagnosed with COPD.
- Mean adjusted FEV1 decline was 18.7 ml/year in females and 12.7 ml/year in males.
Conclusions:
- ADAM33 SNPs are significantly associated with accelerated lung function decline in the general population.
- These identified ADAM33 SNPs represent genetic risk factors for the development of COPD.