Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disease causing a wide spectrum of autoimmune dysfunction potentially including diabetes of an autoimmune etiology. We have previously described a pair of discordant APECED siblings and pointed to a possible role of 5′insulin variable number of tandem repeats (VNTR) locus IDDM2 in the appearance of diabetes within this disease. In vitro studies have previously suggested that class I VNTR alleles were associated with decreased fetal thymic insulin expression. We genotyped the 5′INS VNTR locus and several flanking 11p15.5 markers in 50 Finnish APECED subjects and explored the possible contribution of IDDM2 in the development of diabetes. The shorter 5′INS VNTR class I alleles (35 repeats) were more prevalent in the diabetic Finnish APECED subjects than in non-diabetic APECED subjects. Logistic regression analysis revealed that having 1 short (35) VNTR allele did not increase the risk of developing diabetes (95% CI 0.6-27.0), whereas having 2 short alleles conferred a 43.5-fold increased risk (95% CI 3.0-634.6). We conclude that short 5′INS VNTR class I alleles play a role in susceptibility to autoimmune diabetes in the context of APECED.

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Genes and Immunity
Department of Pediatrics

Paquette, J., Varin, D., Hamelin, C., Hallgren, Å., Kämpe, O., Carel, J. C., … Deal, C. L. (2010). Risk of autoimmune diabetes in APECED: Association with short alleles of the 5′insulin VNTR. Genes and Immunity, 11(7), 590–597. doi:10.1038/gene.2010.33