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Genetic variants of the HLA-A, HLA-B and AIF1 loci show independent associations with type 1 diabetes in Norwegian families

Genes & Immunity volume 10, pages 141–150 (2009)Cite this article

Abstract

The main genetic predisposition to type 1 diabetes (T1D) is known to be conferred by the HLA-DRB1, -DQA1 and -DQB1 genes in the major histocompatibility complex (MHC). Other genetic factors within this complex are known to contribute, but their identity has often been controversial. This picture is shared with several other autoimmune diseases (AIDs). Moreover, as common genetic factors are known to exist between AIDs, associations reported with other AIDs may also be involved in T1D. In this study, we have used these observations in a candidate gene approach to look for additional MHC risk factors in T1D. Using complementary conditional methods (involving conditional logistic regression and family-based haplotype tests) and analyses of linkage disequilibrium (LD) patterns, we confirmed association for alleles of the HLA-A and HLA-B genes and found preliminary evidence for a novel association of a single-nucleotide polymorphism (rs2259571) in the AIF1 gene, independent of the DRB1-DQA1-DQB1 genes and of each other. However, no evidence of independent associations for a number of previously suggested candidate polymorphisms was detected. Our results illustrate the importance of a comprehensive adjustment for LD effects when performing association studies in this complex.

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Acknowledgements

This study was supported by JDRF Grant 1-2004-793, by the Novo Nordisk Foundation and the Norwegian Diabetes Association. M Olsson was supported by SSF Grant A3 02:129. We thank CIGENE, Ås, Norway, for performing the genotyping with the SNPlex and MassARRAY assays and Linda Haugse for assistance in HLA genotyping. This research utilizes resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD) and Juvenile Diabetes Research Foundation International (JDRF) and supported by U01 DK062418.

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Authors and Affiliations

  1. Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway

    M C Eike, E Thorsby & B A Lie

  2. Faculty Division Rikshospitalet, Institute of Immunology, University of Oslo, Oslo, Norway

    M C Eike & E Thorsby

  3. Mathematical Statistics, Chalmers University of Technology, Gothenburg, Sweden

    M Olsson

  4. Faculty Division Ullevål University Hospital, Institute of Medical Genetics, University of Oslo, Oslo, Norway

    D E Undlien

  5. Department of Medical Genetics, Ullevål University Hospital, Oslo, Norway

    D E Undlien

  6. Department of Paediatrics, Ullevål University Hospital, Oslo, Norway

    K Dahl-Jørgensen & G Joner

  7. Faculty of Medicine, University of Oslo, Oslo, Norway

    K Dahl-Jørgensen

  8. Institute of Health Management and Health Economics, University of Oslo, Oslo, Norway

    G Joner

  9. Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway

    K S Rønningen

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  1. M C Eike
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Correspondence to M C Eike.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Eike, M., Olsson, M., Undlien, D. et al. Genetic variants of the HLA-A, HLA-B and AIF1 loci show independent associations with type 1 diabetes in Norwegian families. Genes Immun 10, 141–150 (2009). https://doi.org/10.1038/gene.2008.88

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