Published ahead of print on April 19, 2007, doi:10.1164/rccm.200611-1723OC
© 2007 American Thoracic Society doi: 10.1164/rccm.200611-1723OC
The SERPINE2 Gene Is Associated with Chronic Obstructive Pulmonary Disease in Two Large Populations1 GlaxoSmithKline, Research Triangle Park, North Carolina; 2 University of Bergen, Bergen, Norway; 3 Cambridge Institute for Medical Research, Cambridge, United Kingdom; and 4 Brigham and Women's Hospital, Boston, Massachusetts Correspondence and requests for reprints should be addressed to Sreekumar G. Pillai, Ph.D., GlaxoSmithKline R&D, 5 Moore Drive, Research Triangle Park, NC 27709. E-mail: sreekumar.g.pillai{at}gsk.com Rationale: Chronic obstructive pulmonary disease (COPD) is a complex disease influenced by multiple genes and environmental factors. A region on chromosome 2q has been shown to be linked to COPD. A positional candidate gene from the chromosome 2q region SERPINE2 (Serpin peptidase inhibitor, clade E [nexin, plasminogen activator inhibitor type 1], member 2), was previously evaluated as a susceptibility gene for COPD in two association studies, but the results were contradictory. Objectives: To identify the relationship between SERPINE2 polymorphisms and COPD-related phenotypes using family-based and case-control association studies. Methods: In the present study, we genotyped 25 single nucleotide polymorphisms (SNPs) from SERPINE2 and analyzed qualitative and quantitative COPD phenotypes in 635 pedigrees with 1,910 individuals and an independent case-control population that included 973 COPD cases and 956 control subjects. The family data were analyzed using family-based association tests. The case-control data were analyzed using logistic regression and linear models.
Measurements and Main Results: Six SNPs demonstrated significant associations with COPD phenotypes in the family-based association analysis (0.0016 Conclusions: These data provide further support for SERPINE2 as a COPD susceptibility gene.
Key Words: chronic obstructive pulmonary disease genetic association, SERPINE2 replication
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