Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Juvenile-onset diabetes mellitus (JDM) is one of the human diseases shown to be associated with histocompatibility antigens. The occurrence of serologically defined HLA antigens B8 Bw15, B18 and Cw3 is increased among these patients (Singal & Blajchman 1973, Nerup et al. 1974, Cudworth & Woodrow 1975). However, lymphocyte defined HLA-D antigens Dw3 and Dw4 (LD 8a and LD w15a), positively associated with these serologically defined antigens, seem to be even stronger markers of susceptibility to this disease (Thomsen et al. 1975).
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PMID:HLA-Dw2 as a marker of resistance against juvenile diabetes mellitus. 7 59

It now appears unequivocal that three markers exist in a linkage group in chromosome 6 of man: HLA-A, HLA-B and PGM3 (Fig. 1.) Tentatively, two other HLA loci and one Ir gene have been mapped close to HLA-B. The probable map order is HLA-A - HLA-C - HLA-B - HLA-D - Ir. The biological functions of these loci are unknown. However, HLA-A, B and C are important in allograft rejection. Other closely linked loci (HDR, CML) appear to be important in the first events of the allograft rejection (first set) and in generation of killer cells. HLA-D might be important in cellular recognition and graft-versus-host reactions (matching at HLA-D decreases the incidence and severity of graft-versus-host disease), and the Ir genes in the defense against infections. HLA-B and HLA-D loci are important markers in studies of disease susceptibility. HLA-B locus antigens HLA-B27 and HLA-B8 are frequently associated with arthritic or autoimmune disorders. HLA-D determinants have been found in association with multiple sclerosis and C2 deficiency (HLA-DW2); juvenile diabetes and Addison's disease (HLA-DW3) and adult type of rheumatoid arthritis (HLA-DW4).
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PMID:Immunogenetic aspects of allotransplantation. 13 74

The discovery of many associations between HLA and human diseases has emphasized the biologic importance of the main histocompatibility system in man. The recent findings from specific immune response genes (Ir locus) mapping within the H2 region of the mouse have led to systematic study of the similar D locus mapping within the HLA region in man. In this study the frequency of a number of HLA-D antigens has been determined in normal individuals and in patients with four diseases selected in view of their genetic background: juvenile diabetes, multiple sclerosis, grass pollinosis and acute leukemia. In each a significant association has been found with a specific HLA-D antigen: DW3 in juvenile diabetes and grass pollinosis, DW2 in multiple sclerosis, and DW7 in acute lymphoblastic leukemia.
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PMID:[HL-A D antigens from B-lymphocytes and susceptibility to certain diseases]. 30 74

In a preliminary study of twenty-three patients with gonadal dysgenesis (Turner's syndrome) and their families, correlation was sought between their serum defined HLA allele frequencies and their known tendencies toward abnormal immune responses and diabetes mellitus, since individuals with the latter disorders have been shown to have an increased frequency of certain HLA types. We were unable to demonstrate an association between these major serum-defined histocompatibility antigens, immune homeostasis disturbances and sex chromosome aneuploidy in this group. It is felt, however, that testing involving the patterns of HLA-D and "HLA-D related" antigen frequencies should be obtained to further evaluate the possibility of such an association.
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PMID:HLA frequencies, diabetes mellitus and autoimmunity in Turner's patients and their relatives. 31 55

We studied the distribution of HLA-D--related (DRw) antigens in 40 patients with juvenile diabetes mellitus (JDM) and 79 matched controls. We found that DRw2 was significantly decreased in the JDM group, suggesting a protective effect of the antigen and that the decrease observed in B7 was secondary. HLA-DRw3 and HLA-DRw4 were increased in the diabetic group, and, as with B8/B15, these two antigen predisposed to the disease additively. The susceptibility for JDM was found to be more strongly related to HLA-DRw3 that to B8. On the other hand, B15 rather than DRw4 showed the stronger association with JDM. Moreover, we found that this second diabetogenic gene is associated primarily with B15 and only secondarily with Cw3, which is in linkage disequilibrium with B15. This study further emphasizes the immunogenetic heterogeneity of JDM.
Diabetes 1979 Jun
PMID:HLA-D--related (DRw) antigens in juvenile diabetes mellitus. 44 15

To study the association of histocompatibility (HLA) genes in black persons with juvenile-onset diabetes, we determined HLA-A, HLA-B, HLA-C and HLA-DR specificities in 40 black Americans with this disease and in 67 unaffected black Americans. Marked increases in the frequencies of HLA-DRw3 and HLA-DRw4 were found in the patients as compared with the unaffected persons: DRw3 was found in 72.5 per cent of patients versus 29.9 per cent of unaffected persons and DRw4 in 72.5 per cent versus 25.4 per cent (corrected P values each less than 0.0007). DRw2 was not found in any of the patients but was present in 26.9 per cent of unaffected persons (P corrected less than 0.035). There is thus a negative correlation between this specificity and juvenile-onset diabetes. By contrast, no meaningful differences were found in the frequencies of A, B, or C locus antigens. Studies in white persons with juvenile-onset diabetes have suggested that the reported HLA-B associations are due to HLA-D region specificities, and our results also support the premise that D region specificities are the primary associations with juvenile-onset diabetes.
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PMID:HLA-DR specificities among black Americans with juvenile-onset diabetes. 48 12

It is well known that certain genes in the HLA-D region confer increased susceptibility to insulin-dependent diabetes mellitus (IDDM). Previous studies have documented an increased risk associated with the HLA-DR beta chain alleles, DR3 and DR4, and the DQ beta chain allele DQB1*0302 (formerly DQw8). Since DQ alpha is also polymorphic and has been strongly implicated as the primary IDDM susceptibility locus in other races, we wanted to assess the contribution of DQ alpha to IDDM in Caucasians. This information would enable us to define more precisely the class II association with IDDM as well as gain insight into issues of cis versus trans association of DQ heterodimers in this disease. To this end, the DQ alpha genotype was determined for a large group of diabetic and normal Caucasian individuals who had been HLA-DQ beta and HLA-DR typed previously. Using the polymerase chain reaction and a set of twelve oligonucleotide probes, we determined the DQ alpha genotype of 323 patients with IDDM and 182 normal subjects. We found that certain DQ alpha alleles are decreased in the diabetic population compared with normal subjects (i.e. DQA1*0102 and *0103), while others are significantly increased in patients with IDDM (i.e. DQA1*0301 and *0501). In addition, certain combinations of DQ alpha alleles are associated with increased susceptibility to disease (i.e. DQA1*0301, *0501). These results parallel our findings at the DQ beta locus; however, because of the various associations between DQ alpha and DQ beta chains, the risks conferred by DQ alpha are generally lower than those at DQ beta. Moreover, our data indicate that, in Caucasians, no single DQ alpha allele accounts for the highest degree of susceptibility to IDDM as in other races, although DQ alpha analysis may be informative in a few cases. When done in combination, however, oligonucleotide analyses at both DQ alpha and DQ beta complement each other and provide a more complete assessment of the HLA-associated component of disease susceptibility in IDDM.
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PMID:Analysis of HLA genotypes and susceptibility to insulin-dependent diabetes mellitus: HLA-DQ alpha complements HLA-DQ beta. 150 99

The association of certain HLA-D alleles with insulin-dependent diabetes mellitus (IDDM) is well known. One hundred and sixty-one non-related diabetic individuals and 142 non-related healthy controls were typed for the HLA DR-DQw-Dw association, using a restriction fragment length polymorphism (RFLP) typing method that combines three probe/enzyme systems: DRB/Taq I, DQB/Taq I, and DQB/Bam HI. Comparison of frequencies in both diabetics and controls confirms previous results in terms of HLA class II and IDDM association. Moreover, we have found that DR3/3 heterozygous individuals are more susceptible to IDDM when they are also Dw25 (associated with B18) than when they are Dw24 (associated with B8). Using oligonucleotide dot-blot hybridizations we analyzed the HLA-DQB1 sequence of DR3,Dw24 and DR3,Dw25 homozygous individuals, and we found no difference at position 57 between these two DR3-carrying haplotypes. This observation points to the heterogeneity of HLA genetic factors in IDDM susceptibility.
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PMID:Heterogeneity of HLA genetic factors in IDDM susceptibility. 197 Mar 33

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

Transracial analysis provides a method of distinguishing primary associations between insulin-dependent diabetes mellitus (IDDM) and HLA class II alleles from those secondary to linkage disequilibrium. Blacks show DR-DQ relationships that are different from other races and are a useful group in which to investigate HLA-D region associations with IDDM. In this study, the frequencies of HLA-DQA1 and -DQB1 alleles in Afro-Caribbean IDDM and control subjects were compared. Alleles were identified with sequence-specific oligonucleotide probing. The DQA1 allele A3 was positively associated with IDDM (relative risk [RR] = 25.3, corrected P [Pc] less than 7.0 x 10(-6). The DQB1 alleles DQw2 and DQw8 were also positively associated (RR = 4.7, Pc less than 6.5 x 10(-3) and RR = 12.3, Pc = 3.4 x 10(-3), respectively). The A1.2 and DQw6 alleles were negatively associated (RR = 0.16, Pc less than 3.5 x 10(-3) and RR = 0.15, Pc = 2.4 x 10(-2), respectively). These findings were compared to data from other races. The positive associations with A3 and DQw2 are consistent with all racial groups investigated. The negative association with DQw6 is present in all racial groups in which it is a common allele. These findings suggest that DQ alleles, and hence DQ molecules, may directly affect predisposition to IDDM.
Diabetes 1991 Jun
PMID:HLA-DQA1 and -DQB1 alleles associated with genetic susceptibility to IDDM in a black population. 204 Mar 90


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