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)

Two hundred subjects with insulin-dependent (type I) diabetes mellitus (IDDM) were typed for HLA-B, HLA-DR, and properdin factor B (Bf). HLA and Bf antigen and haplotype frequencies in subjects were compared with control frequencies derived from the 8th HLA Workshop. Frequencies of extended haplotypes (defined by B-Bf-DR alleles on a chromosome) were also contrasted with control frequencies. Significant positive associations between IDDM and HLA-B8, DR3, DR4, BfS, and BfF1 were confirmed, as were significant negative associations between IDDM and HLA-B7, DR2, DR5, DR7, and BfF. One haplotype (B7-BfS-DR2) exhibited significant negative association, while five haplotypes (B8-BfS-DR3, B8-BfS-DR4, B15-BfS-DR4, B18-BfF1-DR3, and B40-BfS-DR4) exhibited significant positive associations with IDDM. In this sample, 64% of all probands carried at least one of the high-risk haplotypes. In conclusion, the occurrence of five "high-risk" haplotypes associated with IDDM provides evidence for previously undocumented genetic heterogeneity and suggests that possibly more than two HLA-region genes may be involved in IDDM susceptibility.
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PMID:Genetic heterogeneity of insulin-dependent (type I) diabetes mellitus: evidence from a study of extended haplotypes. 659 40

HLA phenotypes were studied in 57 Type 2 (non-insulin-dependent) diabetic Papuan patients and the results compared with control subjects of the same Austronesian origin. An association was found between disease and BW62, a split antigen of B15, with corrected probability significant at the 5% level. The frequencies of B13 and BW22 were also increased in diabetic patients but the differences were not statistically significant. Although it has been postulated that Melanesian communities have protection against diabetes, they have a high frequency of BW62, which would imply, from the association found in this study, that susceptibility to Type 2 diabetes has yet to become manifest in them.
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PMID:Type 2 (non-insulin-dependent) diabetes mellitus and HLA antigens in Papua New Guinea. 659 99

We have studied major histocompatibility complex markers in Caucasian patients with type I diabetes mellitus and their families. The frequencies of extended haplotypes that were composed of specific HLA-B, HLA-DR, BF, C2, C4A, and C4B allelic combinations, which occurred more commonly than expected, were compared on random diabetic and normal chromosomes in the study families. We demonstrated that all of the previously recognized increases in HLA-B8, B18, B15, DR3, and perhaps DR4 could be ascribed to the increase among diabetic haplotypes of a few extended haplotypes: [HLA B8, DR3, SC01, GLO2]; [HLA-B18, DR3, F1C30]; [HLA-B15, DR4, SC33]; and [HLA-BW38, DR4, SC21]. In fact, HLA-DR3 on nonextended haplotypes was "protective", with a relative risk considerably less than 1.0. There was a paucity or absence among diabetic patients of several extended haplotypes of normal chromosomes, notably [HLA-B7, DR2, SC31] and [HLA-BW44, DR4, SC30]. The extended haplotype [HLA-BW38, DR4, SC21] is found only in Ashkenazi Jewish patients, which suggests that extended haplotypes mark specific mutations that arise in defined ethnic groups. The data show that no known MHC allele, including HLA-DR3 and possibly HLA-DR4, is per se a marker for or itself a susceptibility gene for type I diabetes. Rather, extended haplotypes, with relatively fixed alleles, are either carriers or noncarriers of susceptibility genes for this disease. Thus, the increased frequency (association) or the decreased frequency (protection) of individual MHC alleles is largely explainable by these extended haplotypes.
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PMID:Extended major histocompatibility complex haplotypes in type I diabetes mellitus. 674 3

The clinical features of 24 patients with coeliac disease and insulin-dependent diabetes mellitus were reviewed. The HLA types of 17 of these patients were compared with those of 44 normal subjects, 49 patients with diabetes only and 58 patients with coeliac disease only. The diagnosis of coeliac disease was made after the diagnosis of diabetes in 14 patients, before diabetes in five and simultaneously in five. In established diabetics, coeliac disease was recognized relatively late (mean age 31 years) but the average duration of symptoms attributable to coeliac disease prior to a jejunal biopsy was five months. Gluten restriction was generally followed by a marked improvement in diabetic control. The frequency of HLA-DR3 in patients with coeliac disease and diabetes mellitus (88 per cent), patients with coeliac disease only (88 per cent), and patients with insulin-dependent diabetes mellitus only (69 per cent), was significantly greater than in normal subjects (44 per cent). The subtype of diabetes related to DR4/B15 does not appear to predispose to coeliac disease. The mechanism of the association between coeliac disease and insulin-dependent diabetes is discussed and the importance of coeliac disease in the differential diagnosis of 'diabetic diarrhoea' is emphasized.
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PMID:Coeliac disease and diabetes mellitus: a study of 24 patients with HLA typing. 675 30

Cytoplasmic islet cell antibodies, as detected by anti-IgG (ICAb), and circulating immune complexes (AgAb), detected by the solid phase C1q test (C1qSP), were evaluated in 153 insulin dependent diabetics (IDD) at diagnosis and subsequently in 88 of these patients who were studied prospectively at regular intervals for up to 3 yr. AgAb detected by the conglutinin (KgBt) and Raji cell (RAJI) techniques were also studied at diagnosis in 34 and 50 diabetics respectively. Normal controls were included in the AgAb studies. Complement fixing islet cell antibodies (CF-ICAb) were evaluated in 30 randomly selected diabetics both at diagnosis and after 6 months. Viral antibodies (VAb) were measured in 30 IDD at diagnosis and in 30 matched controls. Insulin antibodies (IBC) were measured 9 months after diagnosis in 35 diabetics and HLA studies (B8 and B15) performed in 115 patients. In the prospective study the ICAb positivity declined from 50% at diagnosis to 45, 38, 36, 31, 26, 19 and 17% at 1, 3, 6, 9, 12, 24 and 36 months after diagnosis respectively. CF-ICAb were found in 30% of the diabetics at diagnosis and in 23% at 6 months. All patients with CF-ICAb at diagnosis were ICAb positive whilst only 47% of patients with ICAb also had CF-ICAb in the serum. AgAb were found at diagnosis in 35% of patients by C1qSP (p less than 0.001 vs. normals), in 35% by KgBt (p less than 0.001) and in 54% by RAJI (p less than 0.002). Eighty-four patients were studied at diagnosis by more than one AgAb method and of these 57% had at least one positive AgAb result. AgAb by C1qSP declined to less than 20% within 6 months of diagnosis. AgAb, as measured by C1qSP and RAJI techniques, correlated with ICAb at diagnosis whereas there was no correlation with VAb levels, IBC values, nor with the HLA antigens. There was no correlation between AgAb (C1q) and CF-ICAb. HLA B15 positive patients tended to form higher IBC levels than B15 negative patients. Thus, AgAb presence seems to parallel that of ICAb in the early stages of diabetes and both phenomena may be primarily or secondarily involved in the development of the disease.
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PMID:Humoral immunity in type 1 diabetes mellitus: a prospective study. 687 43

It has been of considerable interest to determine if the HLA associations with insulin-dependent diabetes mellitus (IDDM) in blacks are the same as in whites in the United States. Seventy-nine black IDDM patients who were under the age of 40 at onset 283 black controls were HLA typed for A, B and C specificities. This is the largest sample of black IDDM patients yet reported. Analysis of HLA antigen frequencies for these samples has revealed an increased frequency of HLA B8 (p less than 0.01), B3 (p less than 0.02) and B15(p less than 0.006), and a decreased frequency of B14 (p less than 0.01). The estimate of relative risks for B8 and B15 was 2.6 and 4.4, respectively. Comparison of a subsample of the black patients (n = 61) and controls (N = 137) revealed increased frequencies of DR3 (p less than 0.0004), DR4 (p less than 0.0002), and DR7 (p less than 0.03) in the IDDM patients. Both HLA DR2 and DR5 were decreased in the diabetic patients (p less than 0.0001 and p less than 0.0002, respectively). All p values were uncorrected. The associations of HLA antigens with IDDM in our black American sample are essentially the same as those found in white IDDM patients. This suggests that the occurrence of IDDM in American blacks may be due to admixture of white genes.
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PMID:HLA associations with insulin-dependent diabetes mellitus in a sample of the American Black population. 694 6

1. Human leucocyte AB antigens were determined by means of a lymphocyte toxicity test in 84 patients with essential hypertension and in 1000 blood donors. 2. The prevalence of HLA B8 was 16.4% in hypertensive patients and 8.9% in controls (P = 0.07). 3. The prevalence of HLA B12 was 34.5% in hypertensive patients and 26.9% in the control group (N.S.). In WHO stage III hypertension HLA B12 was found in six out of 10 patients. 4. The prevalence of HLA B15 was 1.2% in hypertensive patients and 6.4% in controls (P less than 0.05). 5. In view of a previous report of HLA antigens in Spanish diabetic population, this study does not support the suggestion of a genetic and possibly HLA-linked connection between essential hypertension and diabetes mellitus among the Spanish population. 6. A positive family history of hypertension tended to be more common in those patients with essential hypertension associated with HLA B8.
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PMID:HLA antigens in Spanish patients with essential hypertension. 694 68

Metabolic alterations often accompany the use of OCs (oral contraceptives), especially blood glucose and plasma insulin. Persons at risk have been identified by blood HLA typing and this paper discusses effects of HLA type on carbohydrate metabolic changes accompanying the use of low-dose OCs. The lymphocyte HLA types were determined for the 13 women who were then divided into 2 groups: those at high-risk for insulin-dependent diabetes mellitus (HLA type of B8, B15, AW30; N=6) and those at low-risk (HLA type of B7 or BW35; N=7). Each woman underwent a 3-hour glucose tolerance test before beginning OCs (0.035 mg ethinylestradiol and 0.4 mg norethindrone) and then 6 months following their introduction, with both blood glucose and plasma insulin levels being measured. The high-risk group showed a significantly higher 0.5 hour glucose value and a significant elevation of the 1-hour plasma insulin value in the 6-month test following OC administration. Further study is necessary to determine whether separation of patients into high-risk and low-risk HLA types is important and whether HLA typing to preselect women for certain OC treatment programs is cost-effective.
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PMID:Influence of HLA types on carbohydrate effects of a low-estrogen oral contraceptive. 698 46

Laboratory study fo 109 insulin-dependent diabetics younger than 17 yr of age and resident in greater Montreal at the time on onset of symptoms is reported. The cases were diagnosed during a 2-yr period (1976-1978). Sibling controls were obtained for 72 of the cases studied. Viral titers to coxsackie B, rubella, and mumps virus for the 72 patient-sibling pairs showed no difference in geometric mean titers or in change of titer between samples taken at the time of diagnosis and those taken 28 days later. The incidence of positive islet cell antibody in teh IDdM cases was 68.0% at the time of diagnosis compared with 56.(% 4 wk later. The comparative figures of sibling controls were 4.2% and 1.4%, respectively. The frequency of HLA B8, B15, B18, and B7 antigens were compared both with the sibling controls and a normal control population. Pairing of high risk HLA antigens were found more frequently in cases than controls. There was no difference in geometric mean viral titers in cases with risk risk haplotypes compared with those cases in which such haplotypes were absent.
Diabetes 1981 Jul
PMID:Prospective study of insulin-dependent diabetes mellitus. 701 64

HLA antigens A, B, C, DR and BF were determined in 14 sibling pairs with type I diabetes and in 61 patients without familial risks. Significantly positive associations of the disease with HLA DR3 and DR4 and a negative association with DR2 were found. Positive and negative associations with the various HLA A, B and C antigens (A1, A2, B8, B15, B18, Cw3) are of a secondary nature due to strong genetic coupling with primarily associated DR alleles. Localisation of diabetes-associated genes in the HLA DR region could be demonstrated in two families with HLA recombinations. In both cases the hypothetic disease gene segregated with the HLA DR segment. Joint evaluation of these data in an international series involving 1200 type I diabetics showed furthermore that around 90% of all patients are DR3 and/or DR4 positive, that the highest morbidity risk exists in DR3/4 heterozygosity and that DR4 positive persons usually fall ill before their 20th year of life and frequently in the last 3 months of the year. Allotment of clinical, epidemiological, virological and immunological criteria of type I diabetes to only one of the both risk factors indicates heterogeneous immunopathogenesis of the disease. HLA DR3 predisposes particularly to endocrine autoimmune disease and DR4 to increased virus susceptibility.
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PMID:[HLA association of insulin-dependent diabetes mellitus type I (author's transl)]. 702 Nov 18


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