title: 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: 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.
authors: Blanca E
authors: BE
authors: Himes
authors: Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors: Barbara
authors: B
authors: Klanderman
authors: Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors: John
authors: J
authors: Ziniti
authors: Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors: Jody
authors: J
authors: Senter-Sylvia
authors: Division of Pediatric Pulmonology, Hospital Nacional de Niños, San José, Costa Rica.
authors: Manuel E
authors: ME
authors: Soto-Quiros
authors: Division of Pediatric Pulmonology, Hospital Nacional de Niños, San José, Costa Rica.
authors: Lydiana
authors: L
authors: Avila
authors: Division of Pediatric Pulmonary Medicine, Allergy and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors: Juan C
authors: JC
authors: Celedón
authors: Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors: Christoph
authors: C
authors: Lange
authors: Division of Neonatology and Center for Pediatric Biomedical Research, University of Rochester, Rochester, NY.
authors: Thomas J
authors: TJ
authors: Mariani
authors: Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors: Jessica
authors: J
authors: Lasky-Su
authors: Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors: Craig P
authors: CP
authors: Hersh
authors: Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors: Benjamin A
authors: BA
authors: Raby
authors: Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors: Edwin K
authors: EK
authors: Silverman
authors: Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors: Scott T
authors: ST
authors: Weiss
authors: Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors: Dawn L
authors: DL
authors: DeMeo
mesh_terms: D001249:Asthma / Q000235:genetics*; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics; D015842:Serine Proteinase Inhibitors / Q000235:genetics*; D058258:Serpin E2 / Q000235:genetics*
chemical_list: C545486:SERPINE2 protein, human; D015842:Serine Proteinase Inhibitors; D058258:Serpin E2