Association of SERPINE2 with asthma.

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.

• Authors: Blanca E Himes, Barbara Klanderman, John Ziniti, Jody Senter-Sylvia, Manuel E Soto-Quiros, Lydiana Avila, Juan C Celedón, Christoph Lange, Thomas J Mariani, Jessica Lasky-Su, Craig P Hersh, Benjamin A Raby, Edwin K Silverman, Scott T Weiss, Dawn L DeMeo
• Journal: Chest (Chest) Vol. 140 Issue 3 Pg. 667-674 (Sep 2011) ISSN: 1931-3543 [Electronic] United States
• PMID: 21436250 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• SERPINE2 protein, human
• Serine Proteinase Inhibitors
• Serpin E2

Topics

• Asthma (genetics)
• Child
• Female
• Genetic Association Studies
• Humans
• Male
• Phenotype
• Polymorphism, Single Nucleotide
• Pulmonary Disease, Chronic Obstructive (genetics)
• Serine Proteinase Inhibitors (genetics)
• Serpin E2 (genetics)