Gene which predicts wheezing is associated with low vitamin D – Oct 2019

Acute wheeze-specific gene module shows correlation with vitamin D and asthma medication.

Eur Respir J. 2019 Oct 16. pii: 1901330. doi: 10.1183/13993003.01330-2019.

Katayama S1, Hammar KS2,3, Krjutškov K1,4,5, Einarsdottir E1,5,6, Hedlin G2,3, Kere J1,5,7, Söderhäll C8,3.
1 Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
2 Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
3 Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
4 Competence Centre on Health Technologies, Tartu, Estonia.
5 Folkhälsan Institute of Genetics, and Stem Cells and Metabolism Research Program, University of Helsinki, Helsinki, Finland.
6 Current affiliation: SciLifeLab, Department of Gene Technology, KTH-Royal Institute of Technology, Solna, Sweden.
7 School of Basic & Medical Biosciences, King's College London, Guy's Hospital, London, UK.
8 Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden cilla.soderhall at ki.se.

BACKGROUND:
Airway obstruction and wheezing in preschool children with recurrent viral infections are a major clinical problem, and recognised as a risk factor for the development of chronic asthma. We aimed at analyaing whether gene expression profiling provides evidence for pathways that delineate distinct groups of children with wheeze, and in combination with clinical information could contribute to diagnosis and prognosis of disease development.

METHODS:
We analyaed leukocyte transcriptomes from preschool children (6 months-3 y) at acute wheeze (n=107), and at a revisit 2-3 months later, comparing them to age-matched healthy controls (n=66). RNA-sequencing applying GlobinLock was used. The cases were clinically followed until age 7 years. Differential expression tests, weighted correlation network analysis (WGCNA) and logistic regression were applied and correlations to 76 clinical traits evaluated.

FINDINGS:
Significant enrichment of genes involved in the innate immune responses were observed in children with wheeze. We identified a unique acute wheeze-specific gene-module, that was associated with Vitamin D levels (p<0.005) in infancy, and asthma medication and FEV1%/FVC several years later, at age 7 (p<0.005). A model that predicts LTRA-medication at 7 years of age with high accuracy was developed (AUC=0.815, 95% CI: 0.668-0.962).

INTERPRETATION:
Gene expression profiles in blood from preschool wheezers predict asthma symptoms at school-age, and therefore serve as biomarkers. The acute wheeze-specific gene module suggests that molecular phenotyping in combination with clinical information already at an early episode of wheeze may help to distinguish children that will outgrow their wheeze from those that will develop chronic asthma.