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 DMA and DMB genes encode class II-like heterodimetric molecules located in a specialized endocytic compartment, where they facilitate efficient loading of antigenic peptides on HLA class II molecules. Both genes are located within the MHC class II region and present a limited allelic polymorphism. Here we report the distribution of DM alleles in a group of 75 IDDM patients, 72 CD patients, and 162 random controls. We found a pronounced decreased frequency of DMA*0102 in both patient groups relative to controls. This difference was, however, mainly secondary to a strong negative linkage disequilibrium (LD) between this allele and the IDDM and CD-associated DRB1*03 allele. The DMB phenotype frequencies were similar in CD patients and controls. By contrast, we observed a decreased frequency of DMB*0101 and an increased frequency of DMB*0102 and DMB*0104 in IDDM patients. These differences disappeared when matching individuals for DRB1*03 or DRB1*04 alleles, which was in accordance with strong negative LD between DMB*0101 and DRB1*04 or DQB1*0302 alleles, and positive LD between DMB*0104 and DQB1*0201. Our data suggest that the apparent associations of IDDM or CD with given DM alleles are mostly secondary to primary associations with alleles at the DRB and DQB loci.
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PMID:Absence of primary association between DM gene polymorphism and insulin-dependent diabetes mellitus or celiac disease. 883 72

Considerable evidence exists that the genes coding for the HLA class II DQ molecules in the MHC region are major contributors to genetic susceptibility in insulin-dependent diabetes. Located centromeric to the DQ loci are the genes encoding DMA and DMB, two class II-like molecules which play an essential role in the pathway leading to antigen presentation by HLA class II. In this study we have examined the distribution of the DMB allele and studied HLA DQA1-DQB1-TAP2-DMB haplotypes in 52 IDDM families and 65 un-related controls. DMB allele frequencies in IDDM and control subjects were not significantly different. DMB*0101 was present in 85% of patients vs. 76% of controls, DMB*0102 in 12 vs. 17%, DMB*0103 in 3 vs. 5%, DMB*0104 in 0 vs. 2%. The IDDM-susceptible MHC DQA1-DQB1 haplotypes found by analysis of IDDM families were not associated with specific DMB alleles. We conclude that the described DMB polymorphisms are not associated with IDDM susceptibility and DMB genotyping is unlikely to improve the assessment of genetic risk for IDDM.
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PMID:Lack of association of DMB polymorphism with insulin-dependent diabetes. 923 3

The HLA-DMA and HLA-DMB genes are located in the HLA-D region between DQ and DP. Four variants of DMA (DMA*0101-0104) and five of the DMB (DMB*0101-0105) have so far been identified. HLA-DM molecules are required in the process of peptide loading to HLA class II antigens, both regulating the dissociation of class II-associated invariant chain peptides (CLIP) and the subsequent binding of exogenous peptides to HLA class II molecules. In order to investigate the immunogenetic heterogeneity within the HLA-D susceptibility region, we analysed the distribution of DMA alleles in 125 patients with type 1 diabetes mellitus and 90 healthy controls, and of DMB alleles in 102 patients and 89 healthy controls. Patients and controls were all from central Germany. The polymerase chain reaction (PCR) amplified products were purified and separated on a 10% polyacrylamide gel electrophoresis. Among the four recognized DMA alleles, DMA*0102 was significantly less frequent (12% vs. 28.9%, P<0.01) in patients with type 1 diabetes mellitus. DMB*0101 (70.6% vs. 97.8%, P<5.5x10(-3)) was also reduced in frequency compared to controls. Comparing patients and controls positive for the type 1 diabetes high-risk markers we found a significant association between DMA*0102 and DQA*0501 (9.5% vs. 39.1%, P<0.02), as well as DMB*0101 and DQA*0501 (62.5% vs. 96.2%, P<0.03). In conclusion, DMA*0102 and DMB*0101 contribute to genetic protection to type 1 diabetes mellitus in individuals with high-risk DQA markers in the German population.
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PMID:HLA-DMA and HLA-DMB alleles in German patients with type 1 diabetes mellitus. 1051 69

Type 1 diabetes mellitus is a common disease with a complex mode of inheritance. Its aetiology is underpinned by a major locus, insulin-dependent diabetes mellitus 1 (IDDM1) in the human leukocyte antigen (HLA) region of chromosome 6p21, and an unknown number of loci of lesser individual effect. In linkage analyses IDDM1 is a single peak, but it is evident that the linkage is caused by allelic variation of three adjacent genes in a 75 kb region, namely the class II genes, HLA-DRB1, -DQA1 and -DQB1. However, even these three genes may not explain all of the HLA association. We investigated, in the founder population of Sardinia, whether non-DQ/DR polymorphic markers within a 9.452 Mb region encompassing the whole HLA complex further influence the disease risk, after taking into account linkage disequilibrium with the disease loci HLA-DQB1, -DQA1 and -DRB1. We generalized the conditional association test, the haplotype method, to detect marker associations that are independent of the main DR/DQ disease associations. Three regions were identified as risk modifiers. These associations were not only independent of the polymorphic exon 2 sequences of HLA-DQB1, -DQA1 and -DRB1, but also independent of each other. The individual contributions of these risk modifiers were relatively modest but their combined impact was highly significant. Together, alleles of single nucleotide polymorphisms at the DMB and DOB genes, and the microsatellite locus TNFc, identified approximately 40% of Sardinian DR3 haplotypes as non-predisposing. This conditional analysis approach can be applied to any chromosome region involved in the predisposition to complex traits.
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PMID:Conditional linkage disequilibrium analysis of a complex disease superlocus, IDDM1 in the HLA region, reveals the presence of independent modifying gene effects influencing the type 1 diabetes risk encoded by the major HLA-DQB1, -DRB1 disease loci. 1128 54