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.

journal_name

Chest

journal_title

Chest

authors

Himes BE,Klanderman B,Ziniti J,Senter-Sylvia J,Soto-Quiros ME,Avila L,Celedón JC,Lange C,Mariani TJ,Lasky-Su J,Hersh CP,Raby BA,Silverman EK,Weiss ST,DeMeo DL

doi

10.1378/chest.10-2973

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

667-674

issue

3

eissn

0012-3692

issn

1931-3543

pii

S0012-3692(11)60472-8

journal_volume

140

pub_type

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