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The gene region on chromosome 11p15.5 known to be involved in insulin-dependent diabetes mellitus (IDDM) susceptibility was recently mapped to a 4.1-kilobase region including the insulin gene. The region contains 10 candidate polymorphisms that are in strong linkage disequilibrium. By genotyping 7 of these 10 polymorphisms and the tyrosine hydroxylase microsatellite in Finnish Caucasoid IDDM patients and control subjects, we demonstrate that many of the polymorphisms found to be associated with IDDM in other Caucasoid populations do not show any association in this Finnish population. Of the polymorphisms typed, only those at -23 Hph I and the variable number of tandem repeats (VNTR) sites confer significant relative risk. Furthermore, we have demonstrated that the -23 Hph I polymorphism cannot explain the association. Comparison of the genotypic patterns observed here and previously suggests that the VNTR is the most likely candidate for IDDM2. The VNTR is located adjacent to defined regulatory DNA sequences affecting insulin gene expression, which suggests a possible effect on expression of insulin or one of the neighboring genes, tyrosine hydroxylase or insulin-like growth factor 2.

Original publication

DOI

10.2337/diab.44.6.620

Type

Journal article

Journal

Diabetes

Publication Date

06/1995

Volume

44

Pages

620 - 625

Keywords

Chromosome Mapping, Diabetes Mellitus, Type 1, Disease Susceptibility, Finland, Gene Frequency, Genotype, Humans, Insulin, Minisatellite Repeats, Polymorphism, Genetic