Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Rheumatology (Oxford) ; 52(11): 1973-82, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23901134

RESUMO

OBJECTIVE: The MHC exerts the greatest contribution to RA susceptibility, where certain HLA-DRB1 alleles confer the greatest risk. Interestingly, there is evidence for more risk factors in the MHC with regions surrounding the HLA class I loci, but whether these antigen-presenting loci could be causal risk variants has not been directly investigated. In this study we investigate the HLA association by direct genotyping of the HLA loci. METHODS: Nine hundred and fifty RA patients and 933 healthy controls were genotyped for HLA-A, -B and -C. Eleven single-nucleotide polymorphisms (SNPs) and one insertion/deletion in the MHC were also included. Conditional logistic regression analyses were performed separately in ACPA-positive and -negative RA to identify the strongest susceptibility locus and additional risk loci. RESULTS: In ACPA-positive RA, the most significantly associated locus was HLA-DRB1 (P = 1.58 × 10(-54)), with SE alleles being predisposing. After controlling for HLA-DRB1, the HLA-C locus was found to confer susceptibility (P = 2.32 × 10(-9)), particularly, the HLA-C*03 allele. Also, in ACPA-negative RA, HLA-DRB1 was the most significant locus (P = 7.22 × 10(-9)), but with other risk alleles (particularly DRB1*03). A possible independent involvement of HLA-C was also observed for ACPA-negative RA (P = 0.02). CONCLUSION: HLA-DRB1 was the major MHC risk locus in both ACPA-positive and ACPA-negative RA, but with allelic risk heterogeneity. Joint analyses of the HLA class I loci together with previously proposed SNP associations pointed at HLA-C as a second susceptibility locus in ACPA-positive RA.


Assuntos
Artrite Reumatoide/genética , Autoanticorpos/sangue , Antígenos HLA-C/genética , Cadeias HLA-DRB1/genética , Peptídeos Cíclicos/imunologia , Alelos , Artrite Reumatoide/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Teste de Histocompatibilidade/métodos , Humanos , Polimorfismo de Nucleotídeo Único
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...