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Elevated fractional exhaled nitric oxide and blood eosinophil counts are associated with a 17q21 asthma risk allele in adult subjects

Authors Schwantes EA, Evans MD, Cuskey A, Burford A, Smith JA, Lemanske RF Jr, Jarjour NN, Mathur SK

Received 15 August 2017

Accepted for publication 15 November 2017

Published 19 December 2017 Volume 2018:11 Pages 1—9

DOI https://doi.org/10.2147/JAA.S149183

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Amrita Dosanjh


Elizabeth A Schwantes,1 Michael D Evans,2 Alex Cuskey,1 Alex Burford,1 Judith A Smith,3 Robert F Lemanske Jr,3 Nizar N Jarjour,1 Sameer K Mathur1

1Division of Allergy, Pulmonary and Critical Care, Department of Medicine, 2Department of Biostatistics and Medical Informatics, 3Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

Background and objectives: Genome-wide association studies identified single-nucleotide polymorphisms (SNPs) at the 17q21 locus conferring increased risk for childhood-onset asthma. Little is known about how these SNPs impact adult asthma patients. We sought to examine an adult population for associations between rs7216389 (17q21-associated SNP) and features of asthma including fractional exhaled nitric oxide (FeNO), eosinophil counts, and age of asthma onset.
Methods: Subjects were genotyped at SNP rs7216389. The geometric mean of FeNO measurements and peripheral blood eosinophil counts from 2008 to 2015 were collected. Demographics and medical history were collected including self-reported allergy diagnoses and age of asthma onset. Eosinophils, monocytes, and peripheral blood mononuclear cells (PBMCs) were isolated for the examination of ORMDL3 expression.
Results: FeNO levels from 157 genotyped subjects (31CC, 72CT, and 54TT) and peripheral eosinophil counts from 252 genotyped subjects (46CC, 122CT, and 84TT) were analyzed. In a sub-group analysis of asthma subjects, the number of attributable T alleles was associated with significantly lower age of asthma onset (P=0.03) and greater FeNO levels (geometric mean 30.0 ppb TT, 20.0 ppb CT, 20.0 ppb CC, P=0.02). In the total cohort of subjects, the T allele was associated with a higher percentage of individual eosinophil counts >200/mm3 (45% TT, 26% CT, 24% CC, P=0.005). Eosinophils expressed ORMDL3 mRNA and protein.
Conclusion: In adult subjects, the number of T alleles at SNP rs7216389 corresponds to significantly greater FeNO levels and peripheral eosinophil counts. The expression of ORMDL3 in eosinophils suggests that they may participate in mediating the asthma risk associated with the 17q21 locus.

Keywords: asthma, eosinophils, fractional exhaled nitric oxide, 17q21

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