Pasanen, A., Karjalainen, M. K., Kummola, L., Waage, J., Bønnelykke, K., Ruotsalainen, M., … Rämet, M. (2018). NKG2D gene variation and susceptibility to viral bronchiolitis in childhood. Pediatric Research, 84(3), 451–457. https://doi.org/10.1038/s41390-018-0086-9
NKG2D gene variation and susceptibility to viral bronchiolitis in childhood
|Author:||Pasanen, Anu1; Karjalainen, Minna K.1; Kummola, Laura2;|
1PEDEGO Research Unit, Medical Research Center Oulu, and Department of Children and Adolescents, University of Oulu, Oulu University Hospital, Oulu, Finland
2Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
3COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
4Department of Pediatrics, University of Eastern Finland, Kuopio University Hospital, Kuopio, Finland
5Department of Pediatrics, University of Gothenburg, Queen Silvia Children’s Hospital, Gothenburg, Sweden
6Department of Pediatrics, Seinäjoki Central Hospital, Seinäjoki, Finland
7Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland
8Fimlab Laboratories, Tampere, Finland
9Center for Child Health Research, Tampere University and Tampere University Hospital, Tampere, Finland
10BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland
|Online Access:||PDF Full Text (PDF, 1.3 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2019072923219
|Publish Date:|| 2019-07-29
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.
|Pages:||451 - 457|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3123 Gynaecology and paediatrics
© 2019 Springer Nature Publishing AG. This is a post-peer-review, pre-copyedit version of an article published in Pediatric Researchvolume 84, pages451–457 (2018). The final authenticated version is available online at: https://doi.org/10.1038/s41390-018-0086-9.