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
Chestjournal_title
Chestauthors
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 DLdoi
10.1378/chest.10-2973subject
Has Abstractpub_date
2011-09-01 00:00:00pages
667-674issue
3eissn
0012-3692issn
1931-3543pii
S0012-3692(11)60472-8journal_volume
140pub_type
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