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Evidence for a locus (IDDM16) in the immunoglobulin heavy chain region on chromosome 14q32.3 producing susceptibility to type 1 diabetes

Genes & Immunity volume 3, pages 338–344 (2002)Cite this article

Abstract

Type 1 diabetes results from autoimmune destruction of pancreatic islet β-cells, possibly initiated or exacerbated by viral infections. Recent studies have demonstrated that antibodies towards enterovirus and autoantibodies towards islet cell components develop in the long preclinical phase of type 1 diabetes. We therefore hypothesised that susceptibility to type 1 diabetes could be influenced by genetic factors controlling production of antiviral antibodies or autoantibodies or both. To search for evidence of linkage or association (linkage disequilibrium) between type 1 diabetes and the immunoglobulin heavy chain (IGH) region, 351 North American and British families with ⩾2 diabetic children were genotyped for IGH region microsatellites. Using affected sibpair analysis, significant evidence for linkage was obtained for three markers close to the IGH gene cluster (P values 0.004, 0.002, 0.002). No evidence was found for association using family-based methods. To attempt to confirm these findings, a smaller dataset (241 families, 138 with ⩾2 diabetic children) from Denmark, a more genetically-homogeneous population, was genotyped for one marker only. These families showed no linkage, but significant evidence for association (P = 0.019). This study suggests that a locus (assigned the symbol IDDM16) in the IGH region, possibly an IGH gene, influences susceptibility to type 1 diabetes.

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Acknowledgements

We thank Drs E Colle, H Deane, M Gonthier, J Mahon, R McArthur, R Rodgers, E Ryan, D Stephure, L Stewart, R Trussell and D Wherrett for generously assisting in the collection of Canadian families, E Swiergala and M Engel for laboratory expertise, Tam Lu for computing contributions, R Hodorek for secretarial assistance, and all the families who participated in this research project.

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Authors and Affiliations

  1. Department of Medical Genetics, University of British Columbia, Vancouver, Canada

    L L Field

  2. Steno Diabetes Center, Gentofte, Denmark

    Z Larsen, F Pociot & J Nerup

  3. Department of Medical Genetics, University of Calgary, Calgary, Canada

    R Tobias

  4. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada

    V Bonnevie-Nielsen

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  1. L L Field
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  2. Z Larsen
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  3. F Pociot
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  4. J Nerup
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  5. R Tobias
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  6. V Bonnevie-Nielsen
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Correspondence to L L Field.

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This research was funded by grants to LLF from the Medical Research Council of Canada (No. MT-7910), the Juvenile Diabetes Foundation International (MRC/JDFI Network), and the Network of Centres of Excellence Programme of the Canadian federal government, and grants to FP and JN from the Medical Research Council of Denmark (No. 9802011) and the Juvenile Diabetes Foundation International (No. 998005). The SAGE program package was supported by U.S. Public Health Service Resource Grant 1-P41-RR03655. LLF was an Alberta Heritage Medical Scientist while at the University of Calgary, where some of this research was conducted.

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Field, L., Larsen, Z., Pociot, F. et al. Evidence for a locus (IDDM16) in the immunoglobulin heavy chain region on chromosome 14q32.3 producing susceptibility to type 1 diabetes. Genes Immun 3, 338–344 (2002). https://doi.org/10.1038/sj.gene.6363857

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