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NKG2D gene variation and susceptibility to viral bronchiolitis in childhood.

Journal article
Authors Anu Pasanen
Minna K Karjalainen
Laura Kummola
Johannes Waage
Klaus Bønnelykke
Marja Ruotsalainen
Eija Piippo-Savolainen
Emma Goksör
Kirsi Nuolivirta
Bo Chawes
Nadja Vissing
Hans Bisgaard
Tuomas Jartti
Ilkka Junttila
Göran Wennergren
Mikko Hallman
Matti Korppi
Mika Rämet
Published in Pediatric research
Volume 84
Pages 451–457
ISSN 1530-0447
Publication year 2018
Published at Institute of Clinical Sciences, Department of Pediatrics
Pages 451–457
Language en
Links dx.doi.org/10.1038/s41390-018-0086-...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Pediatrics, Medical Genetics

Abstract

Genetic factors associated with bronchiolitis are inadequately characterized. We therefore inspected a selected subpopulation of our previous genome-wide association study (GWAS) of bronchiolitis for overlap with known quantitative trait loci (QTLs) to identify susceptibility loci that potentially affect mRNA and protein levels.GWAS included a Finnish-Swedish case-control population (n = 187), matched for age and site. We integrated GWAS variants (p < 10-4) with QTL data. We subsequently verified allele-specific expression of identified QTLs by flow cytometry. Association of the resulting candidate loci with bronchiolitis was tested in three additional cohorts from Finland and Denmark (n = 1201).Bronchiolitis-susceptibility variant rs10772271 resided within QTLs previously associated with NKG2D (NK group 2, member D) mRNA and protein levels. Flow cytometric analysis confirmed the association with protein level in NK cells. The GWAS susceptibility allele (A) of rs10772271 (odds ratio [OR] = 2.34) corresponded with decreased NKG2D expression. The allele was nominally associated with bronchiolitis in one Finnish replicate (OR = 1.50), and the other showed directional consistency (OR = 1.43). No association was detected in Danish population CONCLUSIONS: The bronchiolitis GWAS susceptibility allele was linked to decreased NKG2D expression in the QTL data and in our expression analysis. We propose that reduced NKG2D expression predisposes infants to severe bronchiolitis.

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