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)

Type 1 (insulin-dependent) diabetes is less common in Asian Indians than in white Caucasoids. Forty-five Punjabi Asians with Type 1 diabetes and 96 racially matched control subjects were HLA-DR typed. DR3 was increased in diabetic patients vs control subjects (82% vs 38%, p less than 10(-5)) with relative risk 7.7 and etiological fraction 0.72. DR4 was increased in diabetic patients vs control subjects (31% vs 7%, p less than 0.003) with relative risk 5.7 and etiological fraction 0.26. DR2 showed a negative association (relative risk 0.19, etiological fraction -0.28), as did DR7 (relative risk 0.21, etiological fraction -0.33). HLA-DQ beta-chain gene probing using restriction enzyme BamHI in 43 diabetic patients and 90 control subjects showed that the DR1-associated 6.2 and 3.2 kb fragments were less common in diabetic patients than in the control subjects (12% vs 36%, p less than 0.02). A 12 kb fragment was associated with DR4 in both diabetic patients and control subjects. DR3 is the major susceptibility factor for Type 1 diabetes in Punjabi Asians and DR4 is a second marker. Gene probing indicates that the same DR4 subset is associated with the condition as in white Caucasoids. DR1 and its associated DQ beta restriction fragments are reduced in Asian Type 1 diabetic patients making it unlikely that DR1 haplotypes carry a predisposing factor in this racial group. We conclude that the genetic component of Type 1 diabetes in Punjabis shows differences from that of the white Caucasoid population and that the lower frequency of DR4 in this population may contribute to the lower prevalence of Type 1 diabetes.
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PMID:The HLA-D associations of type 1 (insulin-dependent) diabetes in Punjabi Asians in the United Kingdom. 365 60

Eighty-eight North Indian patients with type I, insulin-dependent diabetes mellitus (IDDM) and 113 unaffected individuals were typed for HLA-DR antigens from DR1 to DR7. The frequency of HLA-DR3 was significantly increased in the patients as compared with the controls (78.4% versus 25.7%, corrected P = 1.68 X 10(-12], the relative risk (RR) of 10.52 being much higher than that reported in the Western IDDM population. HLA-DR2 showed a significant negative association (RR = 0.18, corrected P = 1.03 X 10(-5], but DR4 had no relationship with IDDM in the present study (RR = 1.12, P = 0.12). These results emphasize the differences in HLA-IDDM associations among different ethnic groups.
Diabetes 1985 Jun
PMID:HLA-DR antigen frequencies in a North Indian type I diabetic population. 389 68

In an ongoing prospective study 32 individuals have been evaluated for insulin secretory dynamics, islet cell antibodies and HLA antigens, during the preclinical phase of Type 1 diabetes mellitus. Twenty-four out of the 32 subjects were islet cell antibody-positive. To date, 14 subjects (10 islet cell antibody-positive, four islet cell antibody-negative) have progressed to develop overt diabetes. Several patterns of HLA-DR expression were noted (DR3/DR4, DR3/DR3, DR3/x, DR3/DR1, DR4/x, DR4/DR7, DR5/DR7, DR1/DR7 and DR1/DR2). Irrespective of differences in islet cell antibody status or HLA-DR alleles, pre-diabetic individuals exhibited a similar slow course of progressive beta-cell dysfunction.
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PMID:Pre-type 1 (insulin-dependent) diabetes: common endocrinological course despite immunological and immunogenetic heterogeneity. 638 19

A total of 106 pairs of identical twins, of whom 56 were concordant and 50 discordant for insulin-dependent diabetes, were typed for HLA-DR. In both the concordant and discordant groups there was a high prevalence of the antigens DR3 and DR4, a low prevalence of DR5 and DR7, and a virtual absence of DR2. The heterozygous phenotype DR3,DR4 was more prevalent in concordant than discordant pairs. This was therefore the first demonstration of a genetic difference between concordant and discordant identical twin pairs. These findings suggest that possession of both DR3 and DR4 antigens confers a greater genetic predisposition to insulin-dependent diabetes than does the possession of either antigen alone.
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PMID:HLA-DR typing in identical twins with insulin-dependent diabetes: difference between concordant and discordant pairs. 640 59

Segregation of HLA-DR2 among affected and unaffected offspring was studied in 66 HLA-genotypes families with Type 1 diabetes in whom at least one parent carried DR2. The frequency of DR2-positive parents (21%) was not different from that of control families (29%). Among the diabetic probands, the gene frequency of DR2 was significantly decreased compared with control subjects (0.05 versus 0.17, p less than 0.001) as were DR5 (0.07 versus 0.17, p less than 0.01) and DR7 (0.06 versus 0.13, p less than 0.003). Twenty probands carried DR2, in 11 or whom (55%) it was found in combination with either DR3 or DR4. The nine cases who carried another DR allele included one who was DR2 homozygous. Transmission of DR2 was reduced in affected offspring, and random in unaffected siblings, compared with the expected ratio. However, when the DR2 transmission was analysed separately for parents bearing DR2 with DR3, DR4 or another DR allele, it appeared that DR2 transmission to affected offspring was random when the parents carried neither DR3 or DR4, the transmission deficit being due to over-transmission of DR3 and DR4. The haplotype analysis showed that the haplotype A3, Cw7, B7, GfS, DR2, found in 19% of "non-diabetic" DR2 haplotypes was practically absent among "diabetic" DR2-haplotypes (4%). In conclusion, population and segregation analysis could not demonstrate a specific protective effect of DR2.
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PMID:Segregation of HLA-DR2 among affected and non-affected offspring of 66 families with type 1 (insulin-dependent) diabetes. 659 19

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

The DR-locus controlled B-cell antigens were studied in 163 unrelated Spanish coeliac children and 68 families of this group, nine of them with more than one coeliac patient, to obtain more information about the association between these antigens and coeliac disease. The results show that the most common coeliac phenotypes are DR3/DR7, DR7/DR5, DR3/other DR, and DR3/DR3. The family study confirmed the segregation of the disease with the above mentioned phenotypes. In eight of the nine multiple case families, all coeliac children shared both HLA-DR antigens. These findings make it unlikely that a single dominant gene linked to HLA-DR controls the susceptibility to coeliac disease. The phenotypes in the patients were not distributed according to the Hardy-Weinberg equilibrium. Thus, a model based on one recessive susceptibility gene linked to HLA-DR is not probable either. The complexity of the genetics of coeliac disease and some of the features shared with the HLA-DR pattern in juvenile insulin-dependent diabetes are discussed.
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PMID:HLA-DR phenotypes in Spanish coeliac children: their contribution to the understanding of the genetics of the disease. 660 84

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

Eighty-five patients with thalassemia and all available immediate family members were typed for HLA-A,B, C, and DR antigens, and the patients were tested for clinical diabetes and white cell antibodies in response to multiple blood transfusions. The antigen Bw35 was increased among both patients and their parents. This finding is consistent with previous data suggesting that this antigen may offer an independent selective advantage in populations at risk for both thalassemia and malaria. No association of the HLA system to the development of diabetes was noted. A wide variation was observed in the degree of white cell antibody response to transfusions: 25 of the 84 patients tested had significant levels of white cell antibodies while the majority (49) of the patients had essentially no antibodies. The frequency of the antigen DR2 was significantly increased in the high-response group, while the antigens Bw35 and DR7 were significantly increased in the low-response group. This finding suggests that an HLA-linked immune response or immune suppression factor or an HLA-linked susceptibility to iron toxicity may play a role in the development of these antibody responses.
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PMID:HLA-A, B, C, and DR antigen frequencies in relation to development of diabetes and variations in white cell antibody formation in highly transfused thalassemia patients. 695 55

The paper presents data on the cellular and humoral immunity in different periods of insulin-dependent diabetes mellitus (with the disease standing of 0.5 +/- 0.4 years, group A; 3 +/- 1.8 years, group B; and 15 +/- 4 years, group C). Group A patients presented with the immunity system activation: increased counts of T cells, B lymphocytes, T helpers and T inductors, increased share of active T cells (that is, DR positive ones), elevated content of IgM, IgG, IgA (214 +/- 51 mg%, 1200 +/- 124 mg%, 250 +/- 34 mg%, respectively) as against the reference group (156 +/- 74, 914 +/- 387, 189 +/- 49 mg%, respectively) (p < 0.01). In group B patients, who suffered a longer disease, the immunity parameters were within the normal range, and in group C patients, in whom the disease standing was the longest, these shifts were contrary-wise as against those in group A, that is, T and B cell counts were lowered, as were the counts of T-helpers-inductors, Ig levels, and the phagocytosis index was 65 +/- 5 vs. 85 +/- 10% in the controls (p < 0.05), the phagocytosis level being 4 +/- 2 vs. 10 +/- 2 in the controls (p < 0.05). The authors analyze the association of the HLA system characteristics with the immunity shifts. Patients with the HLA A9, B8, B15, B18, DR3, DR4 presented with significant shifts in the immunity status as against those with the HLA A1, A10, B5, B12, B16, B27, DR5, DR7.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Immunologic characterization of patients with insulin-dependent diabetes mellitus with varying duration of disease]. 805 69


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