NKG2D gene variation and susceptibility to viral bronchiolitis in childhood.
Pediatr Res
; 84(3): 451-457, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-29967528
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 populationCONCLUSIONS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bronquiolite Viral
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Predisposição Genética para Doença
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Subfamília K de Receptores Semelhantes a Lectina de Células NK
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Child
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Female
/
Humans
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Infant
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Male
/
Newborn
País/Região como assunto:
Europa
Idioma:
En
Revista:
Pediatr Res
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Finlândia