RØnningen KS, Spurkland A, Tait BD et al. J Clin Invest 85: 1315–1319īaish JM, Weeks T, Giles R, Hoover M, Stastny P, Capra D (1990) Analysis of HLA DQ genotypes and susceptibility in insulin-dependent diabetes mellitus. (1990) A combination of HLA-DQΒ Asp 57-negative and HLA-DQα Arg 52 confers susceptibility to insulin-dependent diabetes mellitus. Proc Natl Acad Sci USA 85: 8111–8115ĭorman JS, LaPorte RE, Stone RA, Trucco M (1990) World-wide differences in the incidence of type I diabetes are associated with amino acid variation at position 57 of the HLA-DQ Β chain.
Morel PA, Dorman JS, Todd JA, McDevitt HO, Trucco M (1988) Aspartic acid at position 57 of the HLA-DQ Β chain protects against type I diabetes: a family study. Todd JA, Bell JI, McDevitt HO (1987) HLA-DQ Β gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. (1988) HLA-DQ rather than HLA-DR region might be involved in dominant non susceptibility to diabetes. Sterkers G, Zeliszewski D, Chausée AM et al. Nepom GT, Erlich H (1991) MHC class II molecules and autoimmunity. Tiwari Jl, Terasaki PI (1985) HLA and disease associations. These findings suggest that the decreased TAP2B allele frequency in Italian IDDM patients is due to HLA DQ haplotype differences between IDDM patients and control subjects, and do not support a contribution to IDDM risk by the TAP2 locus.
Twenty-four unrelated DQA1*0501-DQB1*0201 haplotypes from non-diabetic families had a TAP2B allele frequency (4%) similar to that in IDDM haplotypes. Comparison of transmitted with non-transmitted haplotypes in IDDM families showed a slight but not significant decrease in TAP2B allele frequency on transmitted (3 of 37) vs non-transmitted (2 of 9) HLA DQA1*0501-DQB1*0201 haplotypes. Family haplotype analysis demonstrated linkage disequilibrium between TAP2 and HLA DQA1-DQB1, and showed that the reduced frequency of TAP2B was associated with its absence on the IDDM susceptible DQA1*0301-DQB1*0302 haplotype, its low frequency on DQA1*0501-DQB1*0201, and the association of TAP2B with DQA1*0101-DQB1*0501 haplotypes which were less frequent in IDDM patients. Analysis of 73 informative meiotic events in IDDM and control families demonstrated a recombination fraction between HLA DQB1 and TAP2 loci of 0.041 (Log of the odds score=16.5 p<10 −8) indicating strong linkage between these loci. A decreased frequency of the TAP2B allele was confirmed in this IDDM cohort (12 vs 28% in control subjects, p c<0.05). In order to determine whether the TAP2 locus modulates the risk conferred by HLA DQ loci, HLA DQA1-DQB1-TAP2 haplotypes were analysed in 48 IDDM probands, their first degree relatives, and in 62 normal control subjects.
The TAP2 gene, located in the HLA class II region, encodes a subunit of a transporter involved in the endogenous antigen-processing pathway, and has been suggested to contribute to the genetic risk for insulin-dependent diabetes (IDDM).
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