Evidence for a Type 1 diabetes-specific mechanism for the insulin gene-associated IDDM2 locus rather than a general influence on autoimmunity.

AIMS: The Type 1 diabetes susceptibility locus, IDDM2, has been mapped to a variable number of tandem repeats (VNTR) region 5' upstream of the insulin (INS) and insulin-like growth factor (IGF2) genes on chromosome 11p15. The function of the VNTR is uncertain; however, it may influence the thymic expression of the insulin gene and affect the development of immune self-tolerance. The aim of this study was to investigate whether the INS VNTR region is a Type 1 diabetes-specific locus or acting as a general autoimmunity gene. METHODS: We genotyped the INS-IGF2 VNTR [using the surrogate INS-23 HphI single nucleotide polymorphism (SNP)] in 823 Graves' disease (GD)/multiple sclerosis (MS) families, 1433 GD/MS patients and 837 healthy control subjects. RESULTS: We found no evidence of excess transmission of the allele associated with Type 1 diabetes to individuals affected by GD or MS within the families. Analysis of the case-control dataset showed no genotypic or allelic difference between the two populations. CONCLUSIONS: These data suggest that the INS-IGF2 VNTR is acting as a Type 1 diabetes-specific susceptibility gene rather than as an influence on general autoimmunity.