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

Some alleles of the HLA-DQB1 and DQA1 loci are preferentially associated with susceptibility to type 1 (insulin-dependent) diabetes mellitus (IDDM). Analysis of the HLA-DQ genetic profile may therefore become important for the screening of subjects at risk of IDDM. However ethnic variations in the genetic profile can occur and require background knowledge of the HLA-DQ allelic distribution before screening campaigns. In the present work, HLA-DQA1 and DQB1 genes have been analyzed, after PCR amplification of the genomic DNA, in French and Algerian control subjects (a total of 148) and diabetic patients (a total of 107). Allelic distributions have been investigated in view of a) possible inter-ethnic differences; b) identification of risk and protective alleles and c) the prevalence of DQB1 aspartate 57 negative and DQA1 arginine 52 positive alleles in control and diabetic groups. The DQB1 allelic distribution was similar in both control groups; alleles negative for aspartate at position 57 were 48% in French and 50% in Algerian. In both diabetic groups, the prevalence of alleles negative for aspartate at position 57 was significantly higher: 91% (French) and 81% (Algerian) (p less than 0.001). A majority of patients were homozygote for DQB1 Asp 57 negativity: 83% (French) and 63% (Algerian). The highest relative risk was associated with HLA-DQB1 0201/0302 heterozygosity. The HLA-DQA1 allelic distribution was also similar in French and Algerian controls. Alleles positive for arginine (ARG+) at position 52 were 50% (French) and 57% (Algerian) of controls. In both diabetic groups the prevalence of alleles positive for arginine at position 52 was significantly higher: 78% (French) and 84% (Algerian).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HLA-DQA1 and DQB1 alleles in French and Algerian type 1 diabetic subjects. 168 68

T cell defined epitopes on class II HLA molecules (epitopes distinguishable by T cells but not by antibodies) seem to be important determinants of IDDM susceptibility/resistance. Although HLA-DR4 is associated with IDDM in many populations, DR4-positive HLA haplotypes vary greatly (relative risk from greater than 10 to less than 1). This variation seems to depend on both the DQ allele and T cell defined subtypes of the DR4 allele. These IDDM associated alleles at the two loci (DQB1 and DRB1) are not correlated with each other in the healthy population, so they clearly are independent risk factors. HLA-DR2 has universally been associated with lack of IDDM, and seems to be protective. However, not all DR2 haplotypes protect, and the protection or lack of protection correlates with T cell defined subtypes of DR2. In this case, however, the DR2 subtypes do correlate with DQ alleles, so it is unclear which locus (loci) is (are) actually affecting the disease process. It may be significant that, for both DR2 and DR4, only the more protective subtypes have arginine at amino acid position 71. Other portions of the DR beta chain are clearly important, however. Although TCR alpha and beta seemed to be promising candidates for additional IDDM susceptibility genes, in fact the various TCR alpha and beta haplotypes are equal, or nearly equal, with regard to IDDM susceptibility. The importance of HLA alleles in IDDM susceptibility, and the lack of importance of TCR alpha and beta alleles, may be due to the different means by which the HLA and TCR molecules achieve antigen binding diversity: HLA molecules by multiple loci and allelic diversity, and TCR molecules by the tremendous diversity that can be generated from a single TCR allele during T cell maturation.
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PMID:T cell defined HLA epitopes and T cell receptor polymorphism in insulin dependent diabetes mellitus. 171 35

On the basis of our own studies and those of others, we suggest that several DQ molecules may be involved in IDDM susceptibility (Table 2). Our studies suggest that these DQ molecules may be encoded both when the DQA1 and DQB1 genes are in cis or trans position. A common denominator of several of these IDDM susceptibility molecules is that they have a non-Asp amino acid at DQ beta chain residue 57. Our studies demonstrate that this residue may be an important residue for peptide presentation to T cells.
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PMID:Insulin dependent diabetes mellitus susceptibility or protection may be determined by certain HLA-DQ molecules. 189 71

HLA Class II polymorphisms were analysed in 27 families with at least one Type I diabetic proband using Southern blotting technique according to 10th Histocompatibility Workshop Standards. The probes used were DRB, DQA1, DQB1 and DOB. We have studied 108 haplotypes and performed segregation analysis with HLA serology and restriction fragment length polymorphism (RFLP) data and compared "affected" with "non-affected" haplotypes (not inherited by IDDM patients). RFLPs correlated well with DR and DQ serology and detected additional polymorphisms. In particular, DQB polymorphism analysis showed segregation of the DQw3 splits with 88.5% of the DR4 affected haplotypes bearing the DQw3.2 split (now DQw8) and 11.5% the DQw3.1 split (now DQw7) while in the non-affected DR4 haplotypes 33.3% were DQw3.2 and 66.6% were DQw3.1. Haplotype analysis showed that DR4-DQw3.2 was in strong linkage with the U fragment (2.1 kb Taq I) of DQA2 (DX alpha) and with the L fragment (5.4 kb BamH I) of DOB. This study confirms previous observations of DQB polymorphisms in heterozygous IDDM patients, supports the protective effect of DQw3.1 (DQw7) against the development of the disease and demonstrates the importance of DQw3.2 (DQw8) for susceptibility to Type I diabetes.
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PMID:Restriction fragment length polymorphism analysis of HLA haplotypes in families with type I diabetes mellitus. 196 92

Insulin-dependent diabetes mellitus (IDDM) in Caucasians is closely associated with the HLA-DQ gene, especially the residue 57 of the DQ beta chain. Aspartic acid at this position provides protection against IDDM, and substitution of this residue by alanine, valine or serine increases susceptibility to IDDM. To determine whether this is a common feature of IDDM in different ethnic groups, we studied DQB1 DNA in Japanese patients with IDDM by polymerase chain reaction and non-radioactive restriction site analysis. In contrast to Caucasian patients with IDDM, most Japanese patients with IDDM possessed at least one aspartic acid at position 57 of DQ beta. This finding strongly suggests that aspartic acid at position 57 of DQ beta does not protect the Japanese from IDDM.
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PMID:Aspartic acid at position 57 of the HLA-DQ beta chain is not protective against insulin-dependent diabetes mellitus in Japanese people. 197 Nov 72

New immunogenetic markers are demonstrated for type 1 diabetes mellitus, Graves' disease and Hashimoto's thyroiditis. These markers are detected by restriction fragment length polymorphism (RFLP) analysis of HLA-D region genes and genes for the tumor necrosis factor alpha (TNF alpha). By analysing haplotypes transmitted to diabetic probands in families and comparing them with haplotypes that are only transmitted to healthy siblings it is shown that DQw8-DQB1 gene variation is important for susceptibility on DR4 haplotypes. Analysis of this DQw3 split in patients with Hashimoto's thyroiditis reveals that the other DQB1 gene variation, namely DQw7, displays the strongest association with Hashimoto's thyroiditis. This DQB1 variation has several implications for susceptibility and/or pathogenesis of both autoimmune endocrine diseases. Novel polymorphisms for TNF alpha are detected and it is shown that heterozygosity for TNF polymorphisms is significantly associated with type I diabetes and Graves' disease. Furthermore, DR4 haplotypes transmitted to diabetic probands possess significantly more the 10.5 Kb fragment in contrast to DR4 haplotypes transmitted only to healthy family members. This genetic polymorphism raises functional issues in susceptibility to autoimmune disease and can lead to a new explanation of the enigmatic HLA-association with a variety of diseases.
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PMID:Immunogenetic markers for autoimmune diseases of the endocrine system. 197 65

DNA restriction fragment length polymorphism (RFLP) typing of HLA-DR and DQ alleles of 60 Japanese type 1 (insulin dependent) diabetic patients and 115 controls was performed. RFLP typing of DRB1 showed increased frequency of DR9 and decreased frequencies of DR2 and DRW6 among patients compared to controls. In the RFLP typing of BamHI-digested DNA to DQ beta probe (BamHI-DQB1), the incidence of the 10.26 kb fragment, which represents either DQW4, DQW8 or DQW9, was markedly elevated in the patients, whereas the incidence of DQW6 was reduced. The predicted DR-DQ haplotype study revealed that DR4-DQW4 or DQW8, DRW8-DQW4 or DQW8 and DR9-DQW9 may contribute to susceptibility to type 1 diabetes. When serological typing of the 13 DRW8 patients was performed, all the 11 DRW8 patients carrying DQW4 or DQW8 (BamHI-10.26 kb) were positive for DQW3. These results indicated that the HLA-DQ locus may play an important role in the development of type 1 diabetes in the Japanese as well as other ethnic groups and that the DRW8-DQW8 haplotype may predispose to the disease in Japan.
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PMID:HLA class II (DR, DQ) in Japanese patients with type 1 diabetes mellitus. 198 37

Insulin-dependent diabetes mellitus (IDDM) susceptibility is associated with the DR4-DQw4 haplotype in Japanese and the DR4-DQw8/-Drw8-DQw4 genotype (among others) in whites. We investigated whether these Japanese and white individuals encode the same or a similar DQ alpha beta heterodimer, which may be an IDDM-susceptibility molecule in both populations. First, we carried out genomic DQA1 and DQB1 typing with sequence-specific oligonucleotide probes. The results revealed that Japanese DR4-DQw4 and white DR4-DQw8/DRw8-DQw4 IDDM patients carried the DQA1*0301 allele and the DQB1*0401 or DQB1*0402 allele, either in the cis (Japanese DR4-DQw4 individuals) or trans (white DR4-DQw8/DRw8-DQw4 individuals) position. Because the DQB1*0401 and DQB1*0402 alleles differ only at residue 23, these DQB1 genes are very similar. We next tested cells from these individuals with a particular DQ-specific T-lymphocyte clone, HH58. The clone was only restimulated with cells from Japanese individuals who carried the DQA1*0301 and DQB1*0401 alleles in the cis position or white individuals who carried the DQA1*0301 and DQB1*0402 alleles in the trans position. Thus, particular cis- or trans-encoded DQ alpha beta heterodimers, which in both cases are recognized by T lymphocytes, may confer susceptibility to IDDM in both ethnic groups.
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PMID:Particular HLA-DQ alpha beta heterodimer associated with IDDM susceptibility in both DR4-DQw4 Japanese and DR4-DQw8/DRw8-DQw4 whites. 204 Mar 92

1. The mode of inheritance of the DR3- and DR4-associated susceptibility genotype is essentially recessive, based on both the segregation data and the existence of Hardy-Weinberg equilibrium in Ashkenazi Jewish and possibly in patients of other populations. 2. Maternal effects may alter the expressivity of IDDM in some susceptible offspring, depending on the maternal DR genotype. Thus, the number of susceptible DR4 types inherited from the mothers may be decreased in certain population samples. Conceivably, these maternal effects also account for the smaller proportion of diabetic children born to diabetic women than to diabetic men. Conversely, maternal DRw6 may raise this risk. 3. The locus of the susceptibility gene is most likely in the DQ region. While specific DQA1 and DQB1 alleles are very closely associated with IDDM in some populations, neither is completely associated with it in DR4 haplotypes and neither accounts for the differences in IDDM susceptibility associated with DR3 haplotypes. 4. Linkage disequilibrium between DR and DP alleles in affected haplotypes indicates the existence of subsets of DR3 and DR7, which account for all or most of the risk to those haplotypes. The possibility of direct DP effects is less likely because the respective DP alleles are different and because DR4 does not maintain disequilibrium with DP alleles in either affected or unaffected haplotypes. 5. The DQA2-BglII-7.2Kb polymorphism in complete association with affected B8,DR3 haplotypes suggests the possible involvement of DQA2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HLA and IDDM: facts and speculations on the disease gene and its mode of inheritance. 204 89

This study was carried out in Sardinia, an Italian region with a very high IDDM incidence. HLA class I and class II antigens were studied in 97 unrelated IDDM patients, 33 complete families with at least one affected member each, and 559 healthy controls. Molecular typing of the DQB1 alleles was carried out in 31 patients and 61 controls. The haplotypes were determined by family studies. The HLA-DR3, DQw2, and DR4 antigens were positively associated with IDDM. The DR3 antigen was nearly always associated to B18 and frequently carried by the extended haplotype A30 Cw5 B18 3F130 DR3 DQw2. The genotype analysis of the patients showed a strong increase of the DR3/DR4 heterozygotes with a relative risk higher than that of the DR3 and DR4 homozygotes. The DR2 antigen was negatively associated with IDDM in the central island districts but not in the southern districts. The DQB1 molecular analysis showed only three alleles in the patients: DQB1*0201 (75.8 per cent), DQB1*0302 (16.1 per cent), and DQB1*0502 (8.1 per cent). These alleles are non Asp 57, so it would seem that nearly if not all Sardinian IDDM patients are NA/NA homozygotes. The DQB1*0502 allele, extremely rare in other Caucasian populations, represents in Sardinia about 70 per cent of the HLA-DR2 haplotypes, contributing to the increase of the pool of IDDM susceptible genes. Moreover it is carried in 27 per cent of the DR2 positive individuals with the extended haplotype A2 Cw7 Bw58 3F31 DR2 DQw1.AZH.
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PMID:Serological and molecular studies of HLA in insulin-dependent diabetes mellitus in Sardinia. 210 47


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