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

The major genetic susceptibility to insulin dependent (Type 1) diabetes is determined by genes in the HLA chromosomal region. An increased relative risk for developing the disease is observed in subjects who are HLA A1, A2, B8, B18, B15, B40, CW3, Bfs, DW3, DW4, DRW3, DRW4 positive. There is an additive relative risk in subjects who possess two "high risk" HLA B alleles which has an important influence on the prevalence of the disease in sibships and possibly on the concordance rate in diabetic identical twins. There is also suggestive evidence that particular combinations of "high risk" HLA B alleles are associated with increased or persistent antibody production which may reflect enhanced or differential susceptibility. Certain factors (e.g. HLA B7, DW2 and DRW2) are associated with a significantly reduced risk and may exert a "protective" mechanism in Type I diabetes, by linkage disequilibrium with genes which reduce immune responsiveness. The significant increases and decreases in respect of the HLA B antigens are probably secondary to the corresponding HLA D and DRW associations which reflect a stronger linkage disequilibrium between the genes which determine these specificities and the putative genes which control susceptibility. Initial damage to the beta cells probably occurs a considerable time before the onset of symptoms and theoretically modification of the immune response early in the disease process may reduce the rate of beta cell destruction.
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PMID:Type I diabetes mellitus. 7 36

As suggested from clinical data and on the basis of human leukocyte antigen (HLA) data, insulin-dependent diabetes mellitus (IDDM) is a disease entity in itself and is different from non-insulin-dependent diabetes and other types of diabetes mellitus in aetiology and pathogenesis. HLA-B8 is associated with IDDM in all Caucasian populations studied, irrespective of the age of onset of the disease. HLA-B15 is associated with IDDM in populations of Northern European and British origin, while B18 seems to replace B15 in Southern European populations. IDDM is uncommon in populations where the HLA-B8 frequency is low, and in the Japanese IDDM occurs in association with Bw22. The HLA-Dw3 and Dw4 association with IDDM is stronger than that of the B alleles. Relative risks for B8 and B15 heterozygous and homozygous individuals are identical, i.e., no gene-dose effect exists. The relative risk of B8/B15 carriers is double that of relative risks of B8 and B15 alone, i.e., there are two IDDM-associated genes. The same applies to Dw3/Dw4 carriers. In families the phenotype IDDM segregates with a certain genotype, the diabetic proband's HLA haplotype. Only a small proportion of family members carrying the 'diabetic haplotype' develop IDDM.
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PMID:HLA and insulin-dependent diabetes mellitus. 11 82

HLA antigen typing by lymphocytotoxicity was performed for 2 groups of unrelated caucasian subjects. The first group was composed of 100 subjects with insulin-dependent diabetes mellitus. The second group was composed of 270 healthy subjects without diabetes. Our study has shown that for the inhabitants of Languedoc the BW15 antigen is not the most frequently found (11% of the diabetics, 10% of the healthy subjects) contrary to findings reported by others. The B8 antigen was the most frequently found (20% of the diabetics, 16,3% of the healthy subjects), in agreement with the findings of the same authors. The frequency of BW15 and B8 found simultaneously was increased (observed 3%, expected 1.38%). The principal findings of our study were a significantly increased frequency of Da25 and B18 (23% and 25% for the diabetic subjects, 11.26% and 12.22% for the healthy subjects), and a significantly decreased frequency of A11 and B12 (6% and 18% for the healthy subjects). The association of Da25 and B18 was observed for HLA phenotypes, suggesting a higher incidence of the Da25-B18 haplotype. For the diabetics, the types BW15, BW40 and Da25-B18 have little hereditary character, and are rapidly insulin dependent individuals.
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PMID:HL-A antigens in insulin-dependent diabetes mellitus. 13 29

Insulin-dependent diabetes mellitus, in contrast to non-insulin-dependent diabetes mellitus, is associated with HLA factors B8, BW15, and B18. Recent studies have shown the association to be even stronger with HLA, DW3, and DW4 and have produced evidence for the existence of two "diabetogenic" genes predisposing to insulin-dependent diabetes in different ways. Evidence to suggest the existence of a gene--associated with DW2--that protects against the disease is accumulating. Islet cell antibodies are a feature of insulin-dependent diabetes mellitus and can be seen, in most cases, at the time of diagnosis.
Diabetes 1978
PMID:HLA, islet cell antibodies, and types of diabetes mellitus. 34 16

The study of a hundred and fifteen unrelated insulin-dependent diabetes and eight families with at least two insulin-dependent diabetes members made it possible to confirm the higher frequency of HLA-B8 and B18 (p less than 0.001) among patients, producing a RR of 2.24 and 2.47 respectively. The increased B15 frequency did not achieve statistical significance. B18 whose gametic association (delta = 0.0438) was significant only in diabetic patients was often related to Aw19-2 (Aw30 + Aw31). The B8/B18 genotype gave a relative risk (RR = 4.98) which was significantly higher than that of B8, B18 and B15 heterozygotes (1.50, 1.24 and 1.39 respectively). Pairs of diabetic siblings were more frequently HLA identical than would be expected by chance, and distribution of the pairs of affected sibs into the three categories, identical, semi-identical and different, was closer to the recessive model than to the dominant one. The fact that the B8/B18 individuals had a RR slightly higher than the B8 and B18 homozygotes and distinctly higher than the heterozygotes for only one of these genes, favours the hypothesis of two dominant genes, giving the appearance of recessivity. The gene associated with B18 in Southern Europe seems to play the same part as that of the gene associated with B15 in Northern Europe.
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PMID:Insulin-dependent diabetes and HLA. 39

HLA-B8 and HLA-Bw15, two antigens associated with juvenile diabetes mellitus in Caucasians of North Europe, have a very low frequency in Sardinian population, who nevertheless have a high frequency of diabetes. The association between diabetes and HLA in Sardinian population has therefore been investigated in 60 patients with diabetes, mellitus (32 with juvenile diabetes and 28 with maturity onset diabetes) and 96 normal, unrelated random controls. No disturbance of HLA distributions was found in maturity onset diabetes, but the frequencies of B8 and Bw35 were increased among juvenile diabetics (18.7 percent and 28.1 percent respectively, compared with 2.0 and 11.4 percent in healthy controls). B18 antigen frequency was also increased, although not significantly, in juvenile diabetes mellitus (65.6 percent compared with 50 percent in controls). In contrast the frequency of HLA-Bw15 in two groups of diabetics differed little from that of controls.
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PMID:HLA antigens in Sardinian patients with diabetes mellitus. 59 67

The relationship between HLA antigens and juvenile-onset diabetes mellitus was examined. Tissue typing for HLA antigens was carried out in 77 control subjects and in 133 individuals from 29 families, each of which contained one or more patients with juvenile-onset diabetes. A significant increase in the frequency of B18 antigen was found in the juvenile-onset index cases. In these index cases, the frequency of HLA antigens B8 and B15 was increased and the frequency of B7 and B12 was decreased, but these findings were not significantly different from those in the control subjects. Two examples of recombinations were noted among the 29 families, and in both instances the recombinations were present in the index case. In this selected population of diabetic patients and their first-degree relatives, there were three siblings (6%) who had juvenile-onset diabetes mellitus. This frequency of diabetes in siblings is much more than would be expected in individuals of the same age group. Two nondiabetic siblings had haplotypes identical to those of a diabetic sibling. These nondiabetic siblings may represent prediabetic individuals. The most frequent haplotype noted in diabetic patients and their first-degree relatives was A1, B8, which was present in approximately 25% of the index cases and first-degree relatives.
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PMID:HLA antigens in patients with juvenile diabetes and their first-degree relatives. 73 54

Two hundred and eighty-eight patients with insulin-dependent diabetes w,o were aged 30 or under at onset and 150 patients with late-onset diabetes, 50 of them dependent on insulin and 100 not dependent on insulin, were HLA-typed. There was a significant positive association between the young-onset insulin-dependent patients and HLA-B8, BW15, and B18 and a significant negative association with B7. These data were combined with those from two other centres. There was a significant concordance for the distribution of all the HLA antigens among these three series, producing evidence in favour of an HLA-linked diabetogenic gene (or genes) having a major role in all cases of juvenile-onset insulin-dependent diabetes. There was a positive association between late-onset insulin-dependent diabetes and B8, but no association between non-insulin-dependent diabetes and the HLA system. This provides further evidence for the existence of different pathogenetic mechanisms in the two major clinical forms of diabetes mellitus.
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PMID:Genetic susceptibility in diabetes mellitus: analysis of the HLA association. 99 Jul 15

HLA-A, B, C, DR and DQ typing was performed in 381 Italian insulin-dependent diabetic patients and in 905 normal Italian subjects. The diabetic patients had significantly higher frequencies of HLA-Cw7, B8, B18, DR3, DR4, DQw2 and DQw3 and significantly lower frequencies of HLA-B17, Bw51, DR2, DR7 and DRw11. The frequency of heterozygosity for HLA-DR3/DR4 was significantly higher in patients who developed the disease in the first 2 years of life and DR3+/DR4-, DQw2 and DQw3 alleles were higher in those aged less than 14 years at onset. The HLA-DR4 allele was associated with onset of diabetes in autumn and HLA-B18 with onset in Autumn-winter. Diabetic children who were breast fed had a later onset of insulin-dependent diabetes mellitus than those who were bottle fed but these differences were independent of HLA typing (11.8 +/- 0.72 years vs 9.23 +/- 0.42 years; mean +/- SEM). We conclude that: (1) in general, HLA distribution in Italian insulin-dependent diabetic patients reflects previous data reported in other European and North American populations; (2) HLA-DR3 and DR4 are strongly associated with insulin-dependent diabetes in Italy as well, and these alleles seem to predispose to an earlier onset of the disease; and (3) breast feeding may delay the onset of the disease.
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PMID:HLA-antigens in Italian type 1 diabetic patients: role of DR3/DR4 antigens and breast feeding in the onset of the disease. 157 60


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