ANOMALOUS BEHAVIOR OF THE 5'-INSULIN GENE POLYMORPHISM ALLELE-814 - LACK OF ASSOCIATION WITH TYPE-I DIABETES IN BASQUES

A susceptibility locus (IDDM2) for Type I (insulin-dependent) diabetes mellitus has been idenified as allelic variation at a variable number of tandem repeats polymorphic region upstream of the human insulin ge ne. In Caucasian populations, individuals homozygous for the short len gth alleles (26 to 63 repeats, class I) have a two- to fivefold increa sed risk of developing the disease, while the long alleles (more than 140 repeats: class III) are dominantly protective. Recent evidence has shown that class I alleles ire not equally predisposing, and in parti cular, the 42-repeat allele (allele 814) can be protective when patern ally inherited. We have assessed the contribution of IDDM2 to disease in a group of Basque families with Type I diabetes. As in other Caucas oid populations, we found that class I alleles, as a whole, are associ ated with an increased risk of developing the disease. Using a polymer ase chain reaction-based assay to more accurately resolve the differen t sizes of individual class I alleles, we identified 14 different vari ants and observed that allele 814 has an anomalous behaviour in Basque s, being the only class I allele that does not have an increased frequ ency in the diabetic alleles group. These findings provide additional support for the recently published allele-specific effects of IDDM2 in Type I diabetes pathogenesis.