The HLA-B*39 allele increases type 1 diabetes risk conferred by HLA-DRB1*04:04-DQB1*03:02 and HLA-DRB1*08-DQB1*04 class II haplotypes.
To further characterise the effect of the HLA-B*39 allele on type 1 diabetes risk we assessed its role in different HLA-DR/DQ haplotypes and genotypes using 1764 nuclear families with a diabetic child collected in the framework of the Finnish Paediatric Diabetes Register. HLA assays were based on sequence specific hybridization using lanthanide labelled oligonucleotide probes. Transmissions of major HLA-DR/DQ haplotypes with and without the HLA-B*39 allele to diabetic index cases were analysed by direct haplotype and allele counting. The HLA-B*39 allele significantly increased the disease risk conferred by DRB1*04:04-DQA1*03-DQB1*03:02 and (DR8)-DQB1*04 haplotypes. The same effect was observed on genotype level as disease association for the HLA-B*39 allele was observed in multiple genotypes containing DRB1*04:04-DQA1*03-DQB1*03:02 or (DR8)-DQB1*04 haplotypes. Finally we considered the two common subtypes of the HLA-B*39 allele, B*39:01 and B*39:06 and observed their unequal distribution when stratified for specific DR-DQ haplotypes. The risk for type 1 diabetes conferred by certain DR/DQ haplotypes is modified by the presence of the HLA-B*39 and this confirms the independent disease predisposing effect of the HLA-B*39 allele. The results can be applied in enhancing the sensitivity and specificity of DR/DQ based screening programs for subjects at disease risk.
Immunogenetics Laboratory, University of Turku, Turku, Finland. Electronic address: mlmikk@utu.fi.
M-L
ML
Mikk
Immunogenetics Laboratory, University of Turku, Turku, Finland.
M
M
Kiviniemi
Immunogenetics Laboratory, University of Turku, Turku, Finland.
A-P
AP
Laine
Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
T
T
Härkönen
Department of Pediatrics, Oulu University Hospital, University of Oulu, Oulu, Finland.
R
R
Veijola
Department of Pediatrics, Turku University Hospital, University of Turku, Turku, Finland.
O
O
Simell
Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Department of Pediatrics, Tampere University Hospital, Tampere, Finland; Folkhälsan Research Center, Helsinki, Finland.
M
M
Knip
Immunogenetics Laboratory, University of Turku, Turku, Finland; Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland.
J
J
Ilonen
D000483:Alleles; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005387:Finland; D020022:Genetic Predisposition to Disease; D059946:HLA-B39 Antigen / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D012042:Registries; D017422:Sequence Analysis, DNA
D059946:HLA-B39 Antigen; D059811:HLA-DRB1 Chains
AFBAC; TDT; affected family based control; transmission disequilibrium test