title: Analysis of TAP2 polymorphisms in Finnish individuals with type I diabetes.
abstract: Type I diabetes mellitus is an immune-mediated disease that is known to be associated and linked with genes in the human leukocyte antigen (HLA) region on chromome 6. Functionally, HLA class I antigen presentation may be deranged in type I diabetes. The TAP1 and TAP2 transporters, which mediate the translocation of antigenic peptides into the endoplasmic reticulum and whose genes are located in the HLA class II region, are potential candidates for conferrring predisposition to type I diabetes. Five known coding region variants (codons 379, 565, 651, 665, and 687) as well as three new polymorphisms of TAP2, one silent (codon 604) and two intronic (nucleotide positions 49,270 and 49,471), were typed in a cohort of 146 well-characterized Finnish individuals with type I diabetes and 90 control subjects. Absolute linkage disequilibrium was apparent for the polymorphisms at codons 604, 665, and 687 as well as the two downstream intronic polymorphisms in a 613-bp region of the 3' portion of TAP2; the polymorphism at codon 651, which is also present within this region, was excluded from this linkage. The codon 651 polymorphism defines the allele TAP2F, the frequency of which in HLA-DR4+ diabetic subjects was 5.4 times that in DR4+ controls (27 vs. 5%, p = 0.002, p(c) = 0.01). These data are consistent with the existence of susceptibility haplotypes for type I diabetes in the Finnish population consisting of DRB1*04 (*0401 and *0404), DQ8, and TAP2F.
authors.affiliation: Immunobiology Laboratory, Massachusetts General Hospital-East and Harvard Medical School, Charlestown 02129, USA.
authors.forename: Alfred
authors.initials: A
authors.lastname: Penfornis
authors.forename: Eva
authors.initials: E
authors.lastname: Tuomilehto-Wolf
authors.forename: Denise L
authors.initials: DL
authors.lastname: Faustman
authors.forename: Graham A
authors.initials: GA
authors.lastname: Hitman
mesh_terms: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005387:Finland; D005787:Gene Frequency; D005802:Genes, MHC Class II; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
chemical_list: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D017931:DNA Primers; C071692:TAP2 protein, human