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

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.
 ...
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.
 ...
PMID:HLA and insulin-dependent diabetes mellitus. 11 82

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.
 ...
PMID:Insulin-dependent diabetes and HLA. 39

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

1. The presence of autoantibodies and the histocompatibility leucocyte antigen (HLA) antigen B15 was studied in relation to vascular complications (WHO III) in 148 patients with essential hypertension. 2. Nine of 36 patients with WHO stage III hypertension had autoantibodies, compared with seven out of 78 normotensive controls. 3. The frequency of B15 was 36.1% in hypertensive patients with stage III hypertension and 14.8% in controls. Nine of 18 patients with cerebral complications had B15 and four out of 18 with cardiac complications had B15. 4. The relative risk of vascular complications was 3.4 times higher in B15-positive patients with essential hypertension compared with B15-negative patients. 5. This study suggests that B15-positive patients with essential hypertension represent a subgroup with a higher risk of vascular complications. Long-term studies are needed to determine whether B15 might serve as predictor for vascular complications. 6. The study adds further support to suggestions of a genetic and possibly HLA-linked connection between essential hypertension, diabetes and autoimmunity.
 ...
PMID:Autoantibodies in untreated and treated essential hypertension: relationship to histocompatability leucocyte antigen-B15 and vascular complications. 54 Apr 44

HLA-typing was performed in two groups of juvenile-onset diabetics, one with (n = 58) and one without (n = 109) a family history of the disease. The association of this type of diabetes with certain HLA antigens (excess of B8 and B15, shortage of B7) was confirmed. No heterogeneities could be established between the two groups. This suggests that the aetiologic basis in single and familial cases of juvenile diabetes is the same. The hypothesis, that the B8 associated gene is more penetrant than the B15 associated gene, cannot be confirmed. Haplotypes were determined in families with one and two diabetic siblings. The findings of high haplotype concordance among diabetic siblings was confirmed: concordance of 2, 1 and 0 haplotypes in 7, 5 and 3 pairs respectively. There was a low degree of haplotype concordance between diabetics and nonaffected siblings in the families with two diabetics: 2, 1, and 0 haplotypes in 2, 8 and 6 pairs respectively. This led to the hypothesis of negative selection against these HLA-linked "diabetogenic" genes. This tendency was not, however, observed in families with only one diabetic. The report of a high recombination rate in families with juvenile diabetics could not be confirmed.
 ...
PMID:HLA-typing in juvenile diabetics with and without positive family history and in families with one and two diabetic siblings. 72 Jul 78

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.
 ...
PMID:HLA antigens in patients with juvenile diabetes and their first-degree relatives. 73 54

Association of juvenile diabetes with antigen B8 and B15 was established with the comparison of the phenotype incidence of 28 HLA antigens from locus A and B among 1085 healthy control subjects and 200 patients with diabetes mellitus (74 with juvenile insulin-dependent type and 126 with insulin-independent diabetes in adults). Only the incidence of antigens B15 and Bw 21 was established to be increased in the cases of insulin-dependent type of diabetes in adults. That raises a new interest in the further study of the problem.
 ...
PMID:[HL-A antigens and diabetes mellitus]. 73 32

We studied the distribution of HLA-A, -B, and -C antigens in 94 juvenile-onset diabetic patients and of HLA-DR antigens in 62 of these patients. The frequencies for HLA-B15, -B40, and -Cw3 were significantly increased in the patient group as compared with the control group. With respect to the B-cell specificities, DRw4 was significantly increased in the patients. Analysis of the data to detect the possible presence of primary and secondary associations between HLA alleles and diabetogenic gene(s) indicated that DRw4 possessed a primary association with the diabetogenic gene(s). As a result, B15, B40, and Cw3 possessed secondary associations.
Diabetes 1979 Jan
PMID:Juvenile-onset diabetes HLA-A, -B, -C, and -DR alloantigens. 75 44

One-hundred and seventy-two normotensive, insulin-dependent diabetic patients without clinical proteinuria (Albustix negative) were typed for the major histocompatibility complex class I (HLA-A, -B) and class II (HLA-DR) antigens. Urinary albumin excretion was measured as the albumin:creatinine ratio (UA/UC, mg/mmol) in an early morning sample. Patients expressing the HLA-A2 antigen had significantly higher UA/UC values than those not expressing the antigen. The observed ratio of geometric means was 1.77 (95 per cent confidence interval (CI) 1.18-2.67; p < 0.01); the relative risk of microalbuminuria (UA/UC > 3.0 mg/mmol) associated with expression of HLA-A2 was 2.52 (95 per cent CI 1.11-5.73; p < 0.05). There was no significant association between UA/UC and HLA-B8, -B15, -DR3, -DR4 or other antigens. Patients were re-studied after a mean period of 5.3 years: multiple linear regression analysis showed that the UA/UC at this time was positively related to the initial glycosylated haemoglobin level (p < 0.01) and expression of the HLA-A2 antigen (p < 0.05), but not to blood pressure or creatinine clearance. Fifteen patients developed macroalbuminuria at follow-up (UA/UC > 45.5 mg/mmol). Compared with a group matched for age, sex, duration of diabetes, and glycosylated haemoglobin who did not develop macroalbuminuria, macroalbuminuric patients had a higher frequency of HLA-A2 (p < 0.01). The odds ratio of progressing to macroalbuminuria associated with HLA-A2 had a 95 per cent CI of 1.71 to infinity. We conclude that an immunogenetic factor may play a role in the development of early diabetic nephropathy and that the risk associated with expression of the HLA-A2 antigen is independent of metabolic control and blood pressure.
 ...
PMID:The immunogenetics of early nephropathy in insulin-dependent diabetes mellitus: association between the HLA-A2 antigen and albuminuria. 144 47


1 2 3 4 5 6 7 Next >>