Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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). 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. A decreased frequency of the TAP2B allele was confirmed in this IDDM cohort (12 vs 28% in control subjects, pc < 0.05). 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. 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. 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. No other differences were observed. Twenty-four unrelated DQA1*0501-DQB1*0201 haplotypes from non-diabetic families had a TAP2B allele frequency (4%) similar to that in IDDM haplotypes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HLA DQA1-DQB1-TAP2 haplotypes in IDDM families: no evidence for an additional contribution to disease risk by the TAP2 locus. 758 84

The transporter associated with antigen processing (TAP) encoded in the major histocompatibility complex (MHC) class II region is a molecule required for endogenous antigen processing. We have typed TAP polymorphism in 95 Japanese patients with insulin-dependent diabetes mellitus (DDM) and 75 normal controls. Amino acid substitutions at positions 333 and 637 of TAP1 and at positions 379, 665, and 687 of TAP2 were typed by the polymerase chain reaction (PCR)-sequence-specific oligonucleotide method. In addition, DNA typing of human leukocyte antigen (HLA)-DQA1 and -DQB1 loci was performed by the PCR-restriction fragment length polymorphism method. There was no significant difference between IDDM patients and normal controls in the frequencies of TAP1 and TAP2 alleles. On the contrary, the HLA-DQ locus showed a strong association with IDDM in the same series of subjects. The frequencies of HLA-DQA1*0301 and -DQB1*0401 were increased significantly and those of HLA-DQA1*0103, -DQB1*0501, -DQB1*0601 and -DQB1*0602 were decreased significantly in Japanese IDDM patients compared with normal controls. Positive linkage disequilibrium was observed between HLA-DQB1*0303 and TAP2C and between HLA-DQB1*0401 and TAP2B. Negative linkage disequilibrium was observed between HLA-DQA1*0103 and TAP2A. Even when subjects with HLA-DQA1*0103, -DQA1*0301, -DQB1*0302, -DQB1*0303, and -DQB1*0401 were considered separately, no significant differences was found in the distribution of TAP1 and TAP2 alleles between IDDM patients and normal controls. We conclude that it is not TAP but HLA-DQ that exhibits a primary association with Japanese IDDM.
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PMID:Lack of association of the transporter associated with antigen processing with Japanese insulin-dependent diabetes mellitus. 805 40