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Hum Immunol. 2014 Jan;75(1):65-70. doi: 10.1016/j.humimm.2013.09.008. Epub 2013 Sep 19.

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.

Author information

1
Immunogenetics Laboratory, University of Turku, Turku, Finland. Electronic address: mlmikk@utu.fi.
2
Immunogenetics Laboratory, University of Turku, Turku, Finland.
3
Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
4
Department of Pediatrics, Oulu University Hospital, University of Oulu, Oulu, Finland.
5
Department of Pediatrics, Turku University Hospital, University of Turku, Turku, Finland.
6
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.
7
Immunogenetics Laboratory, University of Turku, Turku, Finland; Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland.

Abstract

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.

KEYWORDS:

AFBAC; TDT; affected family based control; transmission disequilibrium test

PMID:
24055898
DOI:
10.1016/j.humimm.2013.09.008
[Indexed for MEDLINE]

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