title: Anomalous behaviour of the 5' insulin gene polymorphism allele 814: lack of association with Type I diabetes in Basques. GEPV-N Group. Basque-Navarre Endocrinology and Paediatrics.
abstract: A susceptibility locus (IDDM2) for Type I (insulin-dependent) diabetes mellitus has been identified as allelic variation at a variable number of tandem repeats polymorphic region upstream of the human insulin gene. In Caucasian populations, individuals homozygous for the short length alleles (26 to 63 repeats: class I) have a two- to fivefold increased 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 are not equally predisposing, and in particular, the 42-repeat allele (allele 814) can be protective when paternally inherited. We have assessed the contribution of IDDM2 to disease in a group of Basque families with Type I diabetes. As in other Caucasoid populations, we found that class I alleles, as a whole, are associated with an increased risk of developing the disease. Using a polymerase chain reaction-based assay to more accurately resolve the different sizes of individual class I alleles, we identified 14 different variants and observed that allele 814 has an anomalous behaviour in Basques, being the only class I allele that does not have an increased frequency in the diabetic alleles group. These findings provide additional support for the recently published allele-specific effects of IDDM2 in Type I diabetes pathogenesis.
authors.affiliation: Endocrinology and Diabetes Research Group, Hospital de Cruces, Barakaldo-Basque Country, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Urrutia
authors.forename: B
authors.initials: B
authors.lastname: Calvo
authors.forename: J R
authors.initials: JR
authors.lastname: Bilbao
authors.forename: L
authors.initials: L
authors.lastname: Castaño
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic
chemical_list: D007328:Insulin