NKG2D gene variation and susceptibility to viral bronchiolitis in childhood.

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.

• 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, Göran Wennergren, Ilkka Junttila, Mikko Hallman, Matti Korppi, Mika Rämet
• Journal: Pediatric research (Pediatr Res) Vol. 84 Issue 3 Pg. 451-457 (09 2018) ISSN: 1530-0447 [Electronic] United States
• PMID: 29967528 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• KLRK1 protein, human
• NK Cell Lectin-Like Receptor Subfamily K
• RNA, Messenger

Topics

• Alleles
• Bronchiolitis, Viral (genetics)
• Case-Control Studies
• Child
• Chromosome Mapping
• Cohort Studies
• Denmark
• Female
• Finland
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genetic Variation
• Genome-Wide Association Study
• Genotype
• Haplotypes
• Humans
• Infant
• Infant, Newborn
• Killer Cells, Natural (cytology)
• Linkage Disequilibrium
• Male
• NK Cell Lectin-Like Receptor Subfamily K (genetics)
• Odds Ratio
• Phenotype
• Polymorphism, Single Nucleotide
• Quantitative Trait Loci
• RNA, Messenger (metabolism)
• Sweden