Does a central MHC gene in linkage disequilibrium with HLA-DRB1*0401 affect susceptibility to type 1 diabetes?
Genes Immun
; 6(4): 298-304, 2005 Jun.
Article
en En
| MEDLINE
| ID: mdl-15858601
ABSTRACT
Subtypes of HLA-DR4 are associated with susceptibility or protection against type 1 diabetes (T1DM). We addressed whether this reflects linkage disequilibrium with the true susceptibility locus by studying broader MHC haplotypes marked by alleles of HLA-B, IKBL (adjacent to TNFA) and complement C4. The study used a largely Caucasian cohort from Western Australia. HLA-DRB1*0401 and HLA-DRB1*0405 marked susceptibility to T1DM. In Caucasians, DRB1*0401 occurs predominantly in the 44.1 ancestral haplotype (AH; HLA-A2,B44, DRB1*0401,DQB1*0301) and the 62.1AH (HLA-A2,B15(62),DRB1*0401,DQB1*0302). HLA-B15 marked susceptibility and HLA-B44 marked with resistance to T1DM in patients and controls preselected for HLA-DRB1*0401. A gene between TNFA and HLA-B on the 8.1AH (HLA-A1,B8,;DR3,DQ2) modifies the effects of the class II alleles. Here, alleles characteristic of the 62.1AH (C4B3, IKBL+446*T and HLA-A2,B15) were screened in donors preselected for HLA-DRB1*0401. C4B3 was associated with diabetes, consistent with a diabetes gene telomeric of MHC class II. However, increases in carriage of IKBL+446*T and HLA-A2,B15 were marginal, as too few control subjects were available with the diabetogenic alleles. However, with these tools, selection of HLA-DRB1*0401, DQB1*0302 donors who are positive and negative for C4B3 will allow bidirectional mapping of diabetes genes in the central MHC.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antígenos HLA-DR
/
Desequilibrio de Ligamiento
/
Predisposición Genética a la Enfermedad
/
Diabetes Mellitus Tipo 1
Límite:
Adolescent
/
Child
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Genes Immun
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
BIOLOGIA MOLECULAR
Año:
2005
Tipo del documento:
Article
País de afiliación:
Australia