The SERPINE2 gene is associated with chronic obstructive pulmonary disease in two large populations.
BACKGROUND
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.


OBJECTIVE
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.


RESULTS
Six SNPs demonstrated significant associations with COPD phenotypes in the family-based association analysis (0.0016<or=p<or=0.042). Five of these SNPs demonstrated replicated associations in the case-control analysis (0.021<or=p<or=0.031). In addition, the results of haplotype analyses supported the results from single SNP analyses.


CONCLUSIONS
These data provide further support for SERPINE2 as a COPD susceptibility gene.
Zhu
Guohua
G
GlaxoSmithKline R&D, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
Warren
Liling
L
Aponte
Jennifer
J
Gulsvik
Amund
A
Bakke
Per
P
Anderson
Wayne H
WH
Lomas
David A
DA
Silverman
Edwin K
EK
Pillai
Sreekumar G
SG
D000368:Aged; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D016022:Case-Control Studies; D030541:Databases, Genetic; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D058255:Protease Nexins; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D058258:Serpin E2
D016564:Amyloid beta-Protein Precursor; D058255:Protease Nexins; D011956:Receptors, Cell Surface; C545486:SERPINE2 protein, human; D058258:Serpin E2