RESUMEN
Characterisation of the novel HLA-C*14:02:01:31 allele in a 21-year-old Greek bone marrow donor.
Asunto(s)
Alelos , Exones , Antígenos HLA-C , Secuenciación de Nucleótidos de Alto Rendimiento , Prueba de Histocompatibilidad , Donantes de Tejidos , Humanos , Antígenos HLA-C/genética , Adulto Joven , Trasplante de Médula Ósea , Médula Ósea , Secuencia de Bases , Polimorfismo de Nucleótido Simple , CodónRESUMEN
HLA-C*14:02:01:33 differs from HLA-C*14:02:01:01 by one nucleotide substitution in intron 2.
Asunto(s)
Genes MHC Clase I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Análisis de Secuencia de ADN , Secuenciación de Nucleótidos de Alto Rendimiento , ChinaRESUMEN
HLA-C*14:02:38 differs from HLA-C*14:02:01:01 by one nucleotide at position 288 in exon 2.
Asunto(s)
Pueblo Asiatico , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Pueblo Asiatico/genética , Exones/genética , China , Análisis de Secuencia de ADNRESUMEN
PURPOSE: Phenytoin (PHT) is a common causative drug for severe cutaneous adverse drug reactions (SCARs) in children. SCARs, including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are associated with a variation in HLA genotypes. Blood screening for specific HLA allele before PHT prescription would help in the reduction of the incidence of PHT induced SCARs. This study was to investigate the association between variations of HLA genotypes and PHT induced SCARs in Thai children. METHODS: Cases were Thai children aged between 0-18 years diagnosed with SCARs from PHT. Control groups were Thai children of corresponding age who had taken PHT for a least 12 weeks without any hypersensitivity reaction and healthy population controls. Blood samples from both groups were collected for HLA genotyping using a reverse-sequence specific oligonucleotide (SSO) probes method. Carrier rates of HLA alleles were compared between 22 cases (17 DRESS and 5 SJS-TEN), 60 tolerant controls and 649 population controls. RESULTS: Two HLA alleles includingHLA-B*51:01 and HLA-C*14:02 were significantly associated with PHT induced DRESS (OR 5.83; 95 % CI 1.36-25.00, p = 0.022 and OR 5.85; 95 % CI 1.16-29.35, p = 0.039). HLA-B*38:02 was significantly associated with PHT induced SJS-TEN (OR12.67; 95 % CI 1.50-106.89, p = 0.044). Haplotype analysis demonstrated the association of HLA haplotype A*11:01-B*51:01-C*14:02 and PHT induced DRESS compared to tolerant controls and the healthy population control group (OR 8.92; 95 % CI 1.47-54.02, p = 0.019, and OR 10.2; 95 % CI 3.04-34.21, p = 0.002). HLA haplotype B*38:02-C*07:01 in PHT induced SJS-TEN was significantly higher than those in tolerant controls and the healthy population control group (40 % vs 3.3 % vs 0.3 %; OR 19.33; 95 % CI 1.98-188.59, p = 0.027 and OR 215.67; 95 % CI 22.40-2076.04, p = 0.0003. HLA-B*15:02 was not associated with PHT induced SCARs. SIGNIFICANCE: An association betweenHLA-B*51:01 and HLA-C*14:02 and PHT induced DRESS and HLA-B*38:02 and PHT induced SJS-TEN has been demonstrated in Thai children.
Asunto(s)
Anticonvulsivantes/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/genética , Antígenos HLA/genética , Fenitoína/efectos adversos , Síndrome de Stevens-Johnson/genética , Adolescente , Niño , Preescolar , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Farmacogenética , TailandiaRESUMEN
The HLA-C*14:02:01:03 differs by a single nucleotide at intron 5 (2157 C>T) compared with C*14:02:01:01.
