Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Genes and Immunity |
| Vol/bind | 6 |
| Udgave nummer | 4 |
| Sider (fra-til) | 298-304 |
| Antal sider | 6 |
| ISSN | 1466-4879 |
| DOI | |
| Status | Udgivet - 2005 |
| Udgivet eksternt | Ja |
Bibliografisk note
Keywords: Adolescent; Child; Diabetes Mellitus, Type 1; European Continental Ancestry Group; Female; Genetic Predisposition to Disease; HLA-DR Antigens; Humans; Linkage Disequilibrium; MaleAdgang til dokumentet
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I: Genes and Immunity, Bind 6, Nr. 4, 2005, s. 298-304.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Does a central MHC gene in linkage disequilibrium with HLA-DRB1*0401 affect susceptibility to type 1 diabetes?
AU - Windsor, L
AU - Albert, Mareike
AU - Allcock, R
AU - Scott, A
AU - Sayer, D
AU - Kucharzak, R
AU - Gut, I
AU - McCann, V
AU - Davis, E
AU - Witt, C
AU - Christiansen, F
AU - Price, P
N1 - Keywords: Adolescent; Child; Diabetes Mellitus, Type 1; European Continental Ancestry Group; Female; Genetic Predisposition to Disease; HLA-DR Antigens; Humans; Linkage Disequilibrium; Male
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
U2 - 10.1038/sj.gene.6364210
DO - 10.1038/sj.gene.6364210
M3 - Journal article
C2 - 15858601
SN - 1466-4879
VL - 6
SP - 298
EP - 304
JO - Genes and Immunity
JF - Genes and Immunity
IS - 4
ER -