The role of the IDDM2 locus in the susceptibility of UK APS1 subjects to type 1 diabetes mellitus

Autoimmune polyendocrinopathy syndrome type 1 (APS1) is characterized by autoimmune destruction of endocrine tissues and chronic mucocutaneous candidiasis. Type 1 diabetes (T1D) affects 12-25% of patients with APS1, and the prediction of whether this complication will affect an individual is not currently possible. However, alleles of a variable number tandem repeat (VNTR) 5' of the insulin gene are known to influence the development of T1D in the general, non-APS1 population. Therefore, we investigated the prevalence of these IDDM2 alleles in British Caucasian patients with APS1. The study employed genotyping of 33 patients with APS1 for the HphI polymorphism that is in tight linkage disequilibrium with the insulin gene VNTR alleles. Thirty-three patients with APS1 were studied, the mean age was 23.5 years and 24% have T1D. Six of eight (75%) APS1 patients with T1D were homozygous for the class I INS VNTR (susceptibility) allele, compared with eight of 25 (32%) of APS1 patients without T1D (P = 0.042). Our data suggest an association between the development of T1D and homozygosity for the T1D susceptibility class IINS VNTR allele in patients with APS1.