Full Paper

Genes and Immunity (2002) 3, 338–344. doi:10.1038/sj.gene.6363857

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

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.

L L Field1, Z Larsen2, F Pociot2, J Nerup2, R Tobias3 and V Bonnevie-Nielsen4

  1. 1Department of Medical Genetics, University of British Columbia, Vancouver, Canada
  2. 2Steno Diabetes Center, Gentofte, Denmark
  3. 3Department of Medical Genetics, University of Calgary, Calgary, Canada
  4. 4Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada

Correspondence: Dr LL Field, Department of Medical Genetics, BC Research Institute for Children’s and Women’s Health, 950 W 28 Avenue, Vancouver, BC, V5Z 4H4, Canada. E-mail: llfield@interchange.ubc.ca

Received 14 December 2001; Revised 23 January 2002; Accepted 24 January 2002.

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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 greater than or equal to2 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 greater than or equal to2 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.

Keywords:

type 1 diabetes; insulin-dependent diabetes; genetics; immunoglobulin heavy chain; antibodies