Refining the association of MHC with multiple sclerosis in African Americans.
Hum Mol Genet
; 19(15): 3080-8, 2010 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-20466734
ABSTRACT
Multiple sclerosis (MS) is a common demyelinating disease of the central nervous system mediated by autoimmune and neurodegenerative pathogenic mechanisms. Multiple genes account for its moderate heritability, but the only genetic region shown to have a large replicable effect on MS susceptibility is the major histocompatibility complex (MHC). Strong linkage disequilibrium (LD) across the MHC has made it difficult to fully characterize individual genetic contributions of this region to MS risk in previous studies. African Americans are at a lower risk for MS when compared with northern Europeans and Americans of European descent, but greater haplotypic diversity and distinct patterns of LD suggest that this population may be particularly informative for fine-mapping efforts. To examine the role of the MHC in African American MS, a case-control association study was performed with 499 African American MS patients and 750 African American controls that were genotyped for 6040 MHC region single nucleotide polymorphisms (SNPs). A replication data set consisting of 451 African American patients and 718 African American controls was genotyped for selected SNPs. Two MHC class II SNPs, rs2647040 and rs3135021, were significant in the replication cohort and partially tagged DRB1*15 alleles. Surprisingly, in comparison to similar studies of individuals of European descent, the MHC seems to play a smaller role in MS susceptibility in African Americans, consistent with pervasive genetic heterogeneity across ancestral groups, and may explain the difference in MS susceptibility between African Americans and individuals of European descent.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Negro o Afroamericano
/
Predisposición Genética a la Enfermedad
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Complejo Mayor de Histocompatibilidad
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Esclerosis Múltiple
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Límite:
Adult
/
Humans
Idioma:
En
Revista:
Hum Mol Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos