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Pediatr Res. 2018 Sep;84(3):451-457. doi: 10.1038/s41390-018-0086-9. Epub 2018 Jun 9.

NKG2D gene variation and susceptibility to viral bronchiolitis in childhood.

Author information

1
PEDEGO Research Unit, Medical Research Center Oulu, and Department of Children and Adolescents, University of Oulu, Oulu University Hospital, Oulu, Finland. anu.pasanen@oulu.fi.
2
PEDEGO Research Unit, Medical Research Center Oulu, and Department of Children and Adolescents, University of Oulu, Oulu University Hospital, Oulu, Finland.
3
Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
4
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
5
Department of Pediatrics, University of Eastern Finland, Kuopio University Hospital, Kuopio, Finland.
6
Department of Pediatrics, University of Gothenburg, Queen Silvia Children's Hospital, Gothenburg, Sweden.
7
Department of Pediatrics, Seinäjoki Central Hospital, Seinäjoki, Finland.
8
Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland.
9
Fimlab Laboratories, Tampere, Finland.
10
Center for Child Health Research, Tampere University and Tampere University Hospital, Tampere, Finland.
11
BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland.

Abstract

BACKGROUND:

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.

METHODS:

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).

RESULTS:

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.

PMID:
29967528
DOI:
10.1038/s41390-018-0086-9
[Indexed for MEDLINE]

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