HLA-C variants associated with amino acid substitutions in the peptide binding groove influence susceptibility to Kawasaki disease.
Hum Immunol
; 80(9): 731-738, 2019 Sep.
Article
em En
| MEDLINE
| ID: mdl-31122742
ABSTRACT
Kawasaki disease (KD) is a pediatric vasculitis caused by an unknown trigger in genetically susceptible children. The incidence varies widely across genetically diverse populations. Several associations with HLA Class I alleles have been reported in single cohort studies. Using a genetic approach, from the nine single nucleotide variants (SNVs) associated with KD susceptibility in children of European descent, we identified SNVs near the HLA-C (rs6906846) and HLA-B genes (rs2254556) whose association was replicated in a Japanese descent cohort (rs6906846 pâ¯=â¯0.01, rs2254556 pâ¯=â¯0.005). The risk allele (A at rs6906846) was also associated with HLA-C*0702 and HLA-C*0401 in both US multi-ethnic and Japanese cohorts and HLA-C*1202 only in the Japanese cohort. The risk A-allele was associated with eight non-conservative amino acid substitutions (amino acid positions); Asp or Ser (9), Arg (14), Ala (49), Ala (73), Ala (90), Arg (97), Phe or Ser (99), and Phe or Ser (116) in the HLA-C peptide binding groove that binds peptides for presentation to cytotoxic T cells (CTL). This raises the possibility of increased affinity to a "KD peptide" that contributes to the vasculitis of KD in genetically susceptible children.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ligação Proteica
/
Sítios de Ligação
/
Antígenos HLA-C
/
Substituição de Aminoácidos
/
Predisposição Genética para Doença
/
Polimorfismo de Nucleotídeo Único
/
Síndrome de Linfonodos Mucocutâneos
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article