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Original Research: ASTHMA |

Association of SERPINE2 With AsthmaAssociation of SERPINE2 With Asthma

Blanca E. Himes, PhD; Barbara Klanderman, PhD; John Ziniti, BA; Jody Senter-Sylvia, MS; Manuel E. Soto-Quiros, MD, PhD; Lydiana Avila, MD; Juan C. Celedón, MD, DrPH; Christoph Lange, PhD; Thomas J. Mariani, PhD; Jessica Lasky-Su, ScD; Craig P. Hersh, MD, MPH; Benjamin A. Raby, MD, MPH; Edwin K. Silverman, MD, PhD; Scott T. Weiss, MD; Dawn L. DeMeo, MD, MPH
Author and Funding Information

From the Channing Laboratory (Drs Himes, Klanderman, Lange, Lasky-Su, Hersh, Raby, Silverman, Weiss, and DeMeo; Mr Ziniti; and Ms Senter-Sylvia), Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; Children’s Hospital Informatics Program (Dr Himes), Boston, MA; Division of Pediatric Pulmonology (Drs Soto-Quiros and Avila), Hospital Nacional de Niños, San José, Costa Rica; Division of Pediatric Pulmonary Medicine (Dr Celedón), Allergy and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA; and Division of Neonatology and Center for Pediatric Biomedical Research (Dr Mariani), University of Rochester, Rochester, NY.

Correspondence to: Blanca E. Himes, PhD, Channing Laboratory, 181 Longwood Ave, Boston, MA 02115; e-mail: blanca.himes@channing.harvard.edu


Funding/Support: The CAMP Genetics Ancillary Study is supported by the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH) [Grants U01 HL075419, U01 HL65899, P01 HL083069, R01 HL086601, and T32 HL07427]. Additional support was provided by the NIH [Grants R37 HL066289, HL04370, R01 HL086601, R01 HL087680 (NHLBI)] and National Library of Medicine [2T15LM007092-16]. Dr DeMeo is supported in part by a Doris Duke Clinical-Scientist Development Award.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;140(3):667-674. doi:10.1378/chest.10-2973
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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 FEV1 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.

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