Analysis of TAP2 polymorphisms in Finnish individuals with type I diabetes

作者：Penfornis A; Tuomilehto Wolf E; Faustman DL^*; Hitman GA

来源：Human Immunology, 2002, 63(1): 61-70.

DOI：10.1016/S0198-8859(01)00365-2

• type I diabetes mellitus
• TAP2 gene
• polymorphisms
• HLA class II
• linkage disequilibrium

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 conferring 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 welt-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.

• 出版日期2002-1