RESUMEN
OBJECTIVE: In addition to the main multiple sclerosis (MS) major histocompatibility complex (MHC) risk allele (HLA DRB1*1501), investigations of the MHC have implicated several class I MHC loci (HLA A, HLA B, and HLA C) as potential independent MS susceptibility loci. Here, we evaluate the role of 3 putative protective alleles in MS: HLA A*02, HLA B*44, and HLA C*05. METHODS: Subjects include a clinic-based patient sample with a diagnosis of either MS or a clinically isolated syndrome (n = 532), compared to subjects in a bone marrow donor registry (n = 776). All subjects have 2-digit HLA data. Logistic regression was used to determine the independence of each allele's effect. We used linear regression and an additive model to test for correlation between an allele and MRI and clinical measures of disease course. RESULTS: After accounting for the effect of HLA DRB1*1501, both HLA A*02 and HLA B*44 are validated as susceptibility alleles (p(A*02) 0.00039 and p(B*44) 0.00092) and remain significantly associated with MS susceptibility in the presence of the other allele. Although A*02 is not associated with MS outcome measures, HLA B*44 demonstrates association with a better radiologic outcome both in terms of brain parenchymal fraction and T2 hyperintense lesion volume (p = 0.03 for each outcome). CONCLUSION: The MHC class I alleles HLA A*02 and HLA B*44 independently reduce susceptibility to MS, but only HLA B*44 appears to influence disease course, preserving brain volume and reducing the burden of T2 hyperintense lesions in subjects with MS.
Asunto(s)
Predisposición Genética a la Enfermedad , Antígenos HLA-B/genética , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/genética , Adulto , Distribución de Chi-Cuadrado , Progresión de la Enfermedad , Femenino , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Genotipo , Antígenos HLA/genética , Antígenos HLA-A/genética , Antígeno HLA-B44 , Antígenos HLA-C/genética , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagen , Evaluación de Resultado en la Atención de Salud , Radiografía , Índice de Severidad de la EnfermedadRESUMEN
Four new DR52-associated DRB1 alleles are described. One allele, DRB1*1130, is a hybrid between a DRB3*02 allele and a DRB1*11011 allele. The other alleles, DRB1*13072, DRB1*1315, and DRB1*1331, are simple reshufflings of known polymorphic motifs.
