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Chest. 2011 Sep;140(3):667-674. doi: 10.1378/chest.10-2973. Epub 2011 Mar 24.

Association of SERPINE2 with asthma.

Author information

1
Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Children's Hospital Informatics Program, Boston, MA. Electronic address: blanca.himes@channing.harvard.edu.
2
Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
3
Division of Pediatric Pulmonology, Hospital Nacional de Niños, San José, Costa Rica.
4
Division of Pediatric Pulmonary Medicine, Allergy and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
5
Division of Neonatology and Center for Pediatric Biomedical Research, University of Rochester, Rochester, NY.

Abstract

BACKGROUND:

The "Dutch hypothesis" suggests that asthma and COPD have common genetic determinants. The serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2 (SERPINE2) gene previously has been associated with COPD. We sought to determine whether SERPINE2 is associated with asthma and asthma-related phenotypes.

METHODS:

We measured the association of 39 SERPINE2 single-nucleotide polymorphisms (SNPs) with asthma-related phenotypes in 655 parent-child trios from the Childhood Asthma Management Program (CAMP), and we measured the association of 19 SERPINE2 SNPs with asthma in a case-control design of 359 CAMP probands and 846 population control subjects. We attempted to replicate primary asthma-related phenotype findings in one independent population and primary asthma affection status findings in two independent populations. We compared association results with CAMP proband expression quantitative trait loci.

RESULTS:

Nine of 39 SNPs had P < .05 for at least one phenotype in CAMP, and two of these replicated in an independent population of 426 people with childhood asthma. Six of 19 SNPs had P < .05 for association with asthma in CAMP/Illumina. None of these replicated in two independent populations. The expression quantitative trait loci revealed that five SNPs associated with asthma in CAMP/Illumina and one SNP associated with FEV(1) in CAMP are strongly correlated with SERPINE2 expression levels. Comparison of results to previous COPD studies identified five SNPs associated with both asthma- and COPD-related phenotypes.

CONCLUSIONS:

Our results weakly support SERPINE2 as a Dutch hypothesis candidate gene through nominally significant associations with asthma and related traits. Further study of SERPINE2 is necessary to verify its involvement in asthma and COPD.

PMID:
21436250
PMCID:
PMC3168857
DOI:
10.1378/chest.10-2973
[Indexed for MEDLINE]
Free PMC Article

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