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

Elizabeth A. Schwantes, Michael D. Evans, Alex Cuskey, Alex Burford, Judith A. Smith, Robert F. Lemanske, Nizar N. Jarjour, Sameer K. Mathur

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalJournal of Asthma and Allergy
Volume11
DOIs
StatePublished - 2018
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank the participants of the study for their dedication to asthma research. Also, we thank the nurses, research coordinators, research laboratory staff, and administrative staff of the University of Wisconsin Allergy and Asthma Research Program, including Paul Fichtinger, Gina Crisafi, Michelle Wolff, Maranda Hyde, Evelyn Falbiene, and Holly Eversoll. In addition, we would like to thank Dr Carole Ober, Dr Emma Thompson, and the laboratory staff at the University of Chicago for assistance with article editing and sample genotyping and Dr Elon Roti Roti at the University of Wisconsin–Madison for assistance with figure preparation and article editing. This study was funded by NIH P01 HL088594, NIH R21 AI122103, and NIH R21 AI121808.

Funding Information:
The authors thank the participants of the study for their dedication to asthma research. Also, we thank the nurses, research coordinators, research laboratory staff, and administrative staff of the University of Wisconsin Allergy and Asthma Research Program, including Paul Fichtinger, Gina Crisafi, Michelle Wolff, Maranda Hyde, Evelyn Falbiene, and Holly Eversoll. In addition, we would like to thank Dr Carole Ober, Dr Emma Thompson, and the laboratory staff at the University of Chicago for assistance with article editing and sample genotyping and Dr Elon Roti Roti at the University of Wisconsin–Madison for assistance with figure preparation and article editing. This study was funded by NIH-National Institutes of Health NIH P01 HL088594, NIH R21 AI122103, and NIH R21 AI121808.

Publisher Copyright:
© 2018 Schwantes et al.

Keywords

  • 17q21
  • Asthma
  • Eosinophils
  • Fractional exhaled nitric oxide

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