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)

We have reported an increased frequency of the rare B3 allotype of the fourth component of complement (C4B3) in insulin-dependent diabetics, especially in those with microangiopathy. This study has now been expanded--20 of 106 subjects with microangiopathy and 9 of 116 without possessed the C4B3 allotype (p less than 0.02). C4B3 is said to be in linkage disequilibrium with HLA-DR4. HLA typing was performed on 94 of these patients, 52 with and 42 without microangiopathy. There was no significant difference in the frequency of DR4 (62 vs 50%), DR3 (65 vs 52%), B8 (40 vs 40%) or B15 (32 vs 19%) respectively between these 2 groups. These results confirm an HLA-linked predisposition to microangiopathy, but do not determine whether the primary association is with C4B3, DR4 or another gene with which they are in linkage disequilibrium.
Diabetes Res 1987 Feb
PMID:HLA and C4 polymorphism in diabetic microangiopathy. 349 90

1. Sixty-five Brazilian, patients with type I, insulin-dependent diabetes mellitus (IDDM) and 100 unaffected individuals were typed for HLA-A, -B, -C and DR antigens. 2. A significantly higher frequency of HLA-A2 (48% of the patients versus 21% of the controls), B15 (20% of the controls), DR3 (57% of the patients versus 28% of the controls) and DR4 (54% of the patients versus 23% of the controls) was found for IDDM patients compared to the controls. 3. In contrast, DR2 (11% of the patients versus 31% of the controls) and DR7 (3% of the patients versus 21% of the controls) were lower in diabetics, but the difference was not significant. 4. The data reported here, when compared with those of other studies, emphasize the ethnic variability in HLA-IDDM associations.
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PMID:Frequency of HLA antigens in a Brazilian type I diabetic population. 350 57

In order to study the heterogeneity of Type 2 (noninsulin-dependent) diabetes, we determined HLA antigens and measured B-cell function as C-peptide response to intravenous glucagon in 217 patients with onset of non-ketotic diabetes after the age of 40 years. Their HLA frequencies were compared with those of Type 1 (insulin-dependent) diabetic patients and of healthy blood donors. The Type 1 diabetic patients showed a typical HLA pattern, with increased frequencies of B15, DR3, DR4, B8/B15 and DR3/DR4 and decreased frequencies of B7 and DR2. The Type 2 diabetic patients could be distinguished from blood donors by increased frequencies of Cw4, DR4, DR5 and DR3/DR4, and from Type 1 diabetic patients by increased frequencies of B7, DR2, DR5 and decreased frequency of A9, Bw22 and DR4. Age at onset and body mass index were unrelated to HLA antigens, but the Type 2 diabetic patients with HLA-Cw4, DR5 and DR6 showed a strong family history for Type 2 diabetes. Type 2 diabetic patients with HLA-B8, DR4, B8/B15 and DR3/DR4 showed significantly lower C-peptide concentrations (p less than 0.05) than patients without these HLA antigens. In contrast, patients with DR5 and DRw8 presented with high C-peptide levels. Twelve patients who were positive for both DR3 and DR4 and 23 patients who were DR3/DR4 negative were followed with repeated C-peptide determinations during a period of three years. The C-peptide concentrations of the DR3/DR4 positive patients decreased during this period, whereas there was no change in C-peptide levels in the DR3/DR4 negative patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between B-cell function and HLA antigens in patients with type 2 (non-insulin-dependent) diabetes. 354 54

In an effort to clarify the mode of inheritance of insulin-dependent diabetes mellitus (IDDM), a total of 230 nuclear families with pointers were analyzed using the computer program COMBIN. Each family was ascertained without deliberate selection for multiplex families, and most families were completely typed for HLA-B, HLA-DR, and properdin factor B (Bf). There were 186 families with normal parents, 44 families with one affected parent, and no families with two affected parents. The computer program COMBIN evaluates evidence for a major locus of disease susceptibility, linkage of the major locus to a known genetic marker locus, linkage disequilibrium between the marker haplotypes and disease susceptibility, pleiotropic effects, and presence of an unlinked modifier. The parameters of COMBIN are T, Q, and D, representing the displacement, gene frequency of the IDDM allele, and dominance, respectively, of the major locus--and TM, QM, and DM being the analogous parameters of the modifier. In addition, the recombination fraction, theta, between the IDDM locus and HLA as well as the coupling frequencies are estimated. Finally, COMBIN simultaneously performs segregation and linkage analysis, with the optimal model being adjusted by the fit to the haplotype sharing distribution of IDDM. The results of these analyses indicated that the best-fitting genetic model of diabetic susceptibility appears to be a single major locus with near recessivity on a scale of standardized genetic liability, with gene frequency of the IDDM susceptibility allele of approximately 14%. In addition, the recombination fraction between the major locus and HLA is zero in all models; that is, for the B-BF-DR haplotype, the IDDM locus is tightly linked, probably (according to data from previous studies) to HLA-DR. Information determined by magnitude of coupling frequencies indicated that there is significant positive linkage disequilibrium with the haplotypes B8-BfS-DR4 and B15-BfS-DR4, significant negative linkage disequilibrium with B7-BfS-DR2, and intermediate disequilibrium for B8-BfS-DR3, B18-BfF1-DR3, and B40-BfS-DR4. Significant evidence in favor of an unlinked (to HLA) modifier (either single major locus or polygenes) could not be demonstrated. In conclusion, genetic susceptibility to IDDM appears to be most consistent with a single major locus with near recessivity that is tightly linked to HLA.
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PMID:A combined segregation and linkage analysis of insulin-dependent diabetes mellitus. 357 73

Jejunal biopsy was performed without selection in 110 of 201 children with insulin-dependent diabetes mellitus; serum reticulin antibody, antigliadin antibody by enzyme-linked immunosorbent assay, and serum IgA were studied in all 201 children. Seven children had severe jejunal villous atrophy, giving a prevalence of celiac disease of at least 3.5%. Of the serum tests used, antigliadin antibody with ELISA was the most sensitive. Four patients adhered to a gluten-free diet, and their jejunal structure became normal; three had subsequent gluten provocation, and the jejunal mucosa relapsed in every one. Six had HLA-B8 and -DR3 antigens, and one had B15 and -DR4 phenotypes. In most patients, a gluten-free diet had little effect on insulin dosage, urinary excretion of glucose, or serum level of hemoglobin A1.
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PMID:Celiac disease in insulin-dependent diabetes mellitus. 370 14

We report a combined segregation and linkage analysis of a Danish sample of 216 insulin-dependent diabetes mellitus (IDDM) nuclear families: of these 216, twenty multiplex families were haplotyped regarding HLA-DR and -B markers. The analysis was conducted using the computer program COMBIN, which includes a modifier to absorb family resemblance that is additional to the effect of the major locus that is assumed linked to a marker locus, eg, within the HLA region. The initial analysis could clearly reject a dominant major locus but could not discriminate between other models with or without modifier. However, after adding supplementary information on population associations between HLA and IDDM together with the identity-by-descent (IBD) distribution to the analysis, a final model was identified. This invokes an additive major locus, linked to HLA with recombination not significantly different from 0, a disease gene frequency of 0.217, plus a dominant modifier. From this model it can be predicted that about 0.15% of the general population is at 100% risk of IDDM, about 5% is at intermediate risk (approximately 10%), while the remaining population has a risk of 0. The model predicts recurrence risks compatible with empirically estimated values. Particularly strong, positive haplotype associations were found for the DR3,B8, DR3,B18, and DR4,B15 haplotypes, but detailed analyses showed that neither these particular haplotypes nor the DR3 and DR4 haplotypes in general could entirely explain the HLA-associated susceptibility. The DR2 haplotypes showed a strong negative association. The results are discussed in the light of available data on the epidemiology of IDDM in order to provide a framework for further epidemiological studies.
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PMID:The genetic susceptibility to insulin-dependent diabetes mellitus: combined segregation and linkage analysis. 386 77

The distribution of major histocompatibility complex (MHC) phenotypes in unrelated patients with Graves' disease or Type I diabetes mellitus and healthy controls was examined. HLA-B8 was increased in both the Graves' disease patients (p = .0018) and diabetes mellitus patients (p = .0246) relative to controls. Although C4A*QO is known to show strong linkage disequilibrium with HLA-B8, we could not demonstrate a difference in the frequency of this allele between either group of patients and the controls because the null C4A*QO cannot be accurately estimated from phenotype data. An unusual variant C4B*3 occurred three times in 117 controls, 10 times in 61 Graves' disease patients (p = .0012) and 13 times in 48 diabetic patients (p = 0.74 X 10(-5]. Although C4B*3 is known to show strong linkage disequilibrium with HLA-B15, the frequencies of B15 in the two patient groups did not differ from that of the controls considered here. When 28 MHC haplotypes (supratypes) from 14 unrelated patients with Type I diabetes were compared with 27 non-diabetes supratypes occurring in the same families but not in the patients, 8/28 Type I diabetes supratypes were C4AQOB1+, HLA-B8+, and 4/28 were C4B*3+, whereas 1/27 non-diabetes supratypes was C4AQOB1+, B8+, and 0/27 was C4B*3+. Of the four C4B*3+ diabetes positive supratypes, two were HLA-B15, one was B5 and one was B40. Finally, the second haplotype of 11 diabetes mellitus patients known to carry one high risk C4 haplotype was investigated. The second haplotype was the common type C4A3B1 in only 3/11, whereas at least 5/11 had second haplotypes containing C4B*QO, C4B*3, C4B*2 or C4A*4.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Polymorphism of the fourth component of complement in Graves' disease and type I diabetes mellitus. 386 86

HLA, A, B and C antigens were determined in 84 South African Indian patients with non-insulin-dependent diabetes mellitus (NIDDM) in whom age of onset was under 35 years and in 760 healthy Indian controls. Increased frequencies of Aw24, B15 and Bw61 were seen in the patients, but the corrected P value was not significant. Among Indians of North Indian origin, however, there was a significant association between B15 and NIDDM (corrected P less than 0,012; relative risk 4,8). In Indians of South Indian origin no clear association with any specific HLA antigens was seen, although there was a slight increase in the frequency of Aw24 (uncorrected P less than 0,007; corrected P greater than 0,05). The findings in this study serve to emphasize the heterogeneity of diabetes mellitus, since no association between NIDDM and HLA antigens has been noted in whites.
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PMID:HLA antigens and non-insulin-dependent diabetes mellitus in young South African Indians. 396 98

The families of 41 probands with type I (insulin-dependent) diabetes mellitus (IDDM) were typed for HLA-A, HLA-B, and HLA-DR antigens in addition to the complement polymorphisms C2, C4A, C4B, and Bf. All of these loci are encoded on the short arm of human chromosome 6 in a narrow region. Alleles at HLA-B (8, 15, 18, and 40), HLA-DR (3 and 4), and Bf (F1) have been associated with increased relative risk (RR) for IDDM, while HLA-B7 and HLA-DR2 have been associated with decreased RR for IDDM. This study confirms those significant risks in addition to confirming increased risk for the null (silent) allele for C4A (C4AQ0) and a rare C4B variant (C4B2.9). The significantly associated antigens (alleles) and risks were: HLA-B8 (RR = 3.1), HLA-DR3 (RR = 5.2), HLA-DR4 (RR = 4.3), and BfF1 (RR = 7.1), in addition to C4AQ0 (RR = 2.8) and C4B2.9 (RR = 12.6). Significantly low risk was associated only with HLA-DR2 (RR = 0.1). In a recent study, we defined five high-risk haplotypes that were determined solely by HLA-B, Bf, and HLA-DR (B8-BfS-DR3, B8-BfS-DR4, B15-BfS-DR4, B18-BfF1-DR3, and B40-BfS-DR4). By inclusion of information from the complement polymorphism, we have defined in greater detail three of these five high-risk haplotypes. One previously identified haplotype (B40-BfS-DR4) showed no complement clustering, while the rare high-risk haplotype (B8-BfS-DR4) was seen only once in this smaller sample.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 May
PMID:Complement and HLA. Further definition of high-risk haplotypes in insulin-dependent diabetes. 398 76

1. The relationship between histocompatibility antigens (HLA) and insulin-dependent diabetes was examined. The relative frequency of HLA and the relative risk were determined for 20 families containing 82 individuals, 23 of whom had insulin-dependent diabetes. The control group contained 102 individuals. 2. The B8, B13, and B15 antigens had the highest relative frequency in the group of diabetic patients, whereas B5, B7 and B12 were lowest. A high relative frequency of histocompatibility antigens was found not only in the diabetic patients, but also in their parents and siblings. There was a predominance of A2B8, A2B15, and A9B15 haplotypes in the diabetic population. The diabetic siblings had identical haplotypes. 3. These data support previous reports suggesting genetic linkage between susceptibility to diabetes and the histocompatibility antigen system.
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PMID:Histocompatibility antigens and insulin-dependent diabetes: a study of 20 Brazilian families. 615 43


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