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) diabetic patients and control subjects of Afro-Caribbean Negroid racial origin were investigated by serological HLA-DR-typing and restriction fragment length polymorphism analysis using DNA probes corresponding to the DQ alpha, DQ beta and DR beta chain genes. Combined analysis indicated that four DR antigens are positively associated with the condition in Negroid subjects - DR3, 4, 7 and w9. DR3 and 4 are also associated in Caucasians, but the relative risk for DR3 is lower in Negroid subjects. The DR7 association is specific for the Negroid race, and DRw9 is only weakly associated in Caucasoid subjects. Restriction fragment length polymorphism analysis demonstrated a DQ beta restriction pattern in Negroid subjects which is absent from Caucasoid subjects. This pattern was associated with DRw9 and a subset of DR7, and was markedly increased in frequency in diabetic patients compared with control subjects (48.7% vs 10.4%, respectively; p less than 10(-4). In the absence of this pattern, DR7 showed no positive association. DR3 in Negroid subjects was associated with two distinct DQ alpha-DQ beta patterns, only one of which was positively associated with diabetes. A DQ beta pattern, in linkage disequilibrium with different DR antigens in different races, conferred a consistent protective effect against the development of Type 1 diabetes. Trans-racial genetic analysis thus supports a primary role for DQ in susceptibility to Type 1 diabetes.
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PMID:Trans-racial studies implicate HLA-DQ as a component of genetic susceptibility to type 1 (insulin-dependent) diabetes. 290 18

Twenty patients with well controlled Type 1 (insulin-dependent) diabetes of at least 10 years duration and 47 control subjects were vaccinated against the hepatitis B virus using the Hevac B vaccine. The vaccine was administered into the deltoid region on three occasions at intervals of 1 month. Thereafter a fourth dose was given to subjects still negative for antibody to hepatitis B surface antigen (HbsAb). The median rise of HbsAb titres was 230 mIU/ml in normal subjects and 50 mIU/ml in diabetic patients (p less than 0.001). Eight patients (40%) failed to reach HbsAb titres above 30 mIU/ml, the level considered to give optimal protection against the infection, whereas only one normal control subject failed to reach this level. Five patients (25%) showed no response despite a fourth dose of the vaccine. There was an increased frequency of HLA-DR7 in low responders and a decreased (less than 1.5) helper/suppressor lymphocyte ratio. Diabetic patients are thus less likely to mount a protective antibody response following vaccination against hepatitis. Since hepatitis B surface antigen is reported to be considerably more common in diabetic patients than control subjects, infection with hepatitis B virus may have a greater risk of chronicity in diabetes.
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PMID:Reduced protection against hepatitis B virus following vaccination in patients with type 1 (insulin-dependent) diabetes. 296 92

Of the HLA allelic associations with insulin-dependent diabetes (IDD) reported to date. DR3 and DR4 have been the most positive and DR2 the most negative. In 952 Caucasian proband patients reported here, only 57 or 6% had no DR3 or DR4 alleles. When these 57 patients were compared to 249 Caucasian controls similarly lacking DR3 and DR4 antigens, there were excesses of DR1 (P = 0.13) and DRW8 (P = 0.01) and deficiencies of DR2 (P = 0.03) and DR5 (P = 0.03) in the patient group. The most common phenotype in this group of patients was DR1/DR7 (12.3%). Only four DR-homozygous patients involving alleles other than DR3 and DR4 were found by genotyping, and all were DR1 homozygotes. Among 506 patients wuth DR3/DRX or DR4/DRX phenotypes, DR1 was more frequent (P = 0.001; Bonferronni P = 0.006), and DR2 (P = 0.001) and DR5 (P = 0.001) less frequent than 243 HLA-matched controls. Of 187 patients with a single DR3 and no DR4, DR1 was more frequent (P = 0.02), with DR2 (P = 0.001) and DR5 (P = 0.02) less frequent than 94 HLA DR-compatible controls. Among 319 patients with a single DR4 but no DR3, DR1 was again more frequent (P = 0.01) and DR2 (P = 0.001) and DR5 (P = 0.001) less frequent than 149 HLA-matched controls. We conclude that DR1 is an additional risk DR allele for IDD to that of DR3 and DR4, and DR5 an additional protective DR allele to that of DR2.
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PMID:Inherited susceptibility to insulin-dependent diabetes is associated with HLA-DR1, while DR5 is protective. 297 18

Some patients do not fall neatly into the categories of Type 1 (insulin-dependent), Type 2 (non-insulin-dependent) or maturity onset diabetes of young people diabetes. The pedigree and characteristics of the family reported here illustrate this problem. Nine cases of diabetes are known in 4 out of 5 generations, with onset between 17-70 years. Treatment was with insulin in 5 (onset 17-29 years), tablets in 3 (onset 32-70 years), and in one diabetes occurred before the insulin era. Plasma C-peptide was 0.04-0.52 nmol/l (fasting) and 0.35-1.33 nmol/l (peak stimulation with glucagon). HLA typing, available in 7 diabetic patients showed DR2 or DR7 in all, DR4 in 2 and DR3 in none. Pancreatic islet cell antibodies were absent at diagnosis in the most recently diagnosed patient. Diabetic complications remain absent in two insulin-treated patients (duration 28 and 24 years), but have occurred extensively in the remainder. The form of diabetes in this family is therefore characterised by (a) strong family history (possible autosomal dominant with variable penetrance), (b) widely variable age of onset, (c) a variable degree of B cell reserve (d) no association with HLA DR3/4 and the presence of DR2 or DR7 and (e) no protection from complications.
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PMID:Familial diabetes mellitus with variable B cell reserve; analysis of a pedigree. 330 4

Class III gene rearrangements have been examined in Thai/Chinese individuals with supratypes bearing defective or null C4 alleles. Genomic DNA from C4 null supratypes was probed with an almost full-length 21-OH probe following digestion with Taq I and Kpn I. The HLA-B17 C4A3 BQ0 BfS DR3 Thai/Chinese supratypes (which may be associated with insulin-dependent diabetes mellitus in Orientals) lacks a 3.2 kb Taq I and a 3.9 kb Kpn I fragment hybridizing with the 21-OH probe. Similar gene rearrangements are found in Caucasoid diabetogenic supratypes HLA-B18 C4A3 BQ0 BfF1 DR3 and HLA-B8 C4AQ0 B1 BfS DR3. Interethnic comparisons suggest that class II and class III interactions may be important in disease susceptibility. By contrast, neither of two Thai/Chinese supratypes with C4AQ0 appear to have major class III gene rearrangements; disease association studies will determine the significance of C4 deficiency per se. As in Caucasoids, the electrophoretically fast C4 allele, C4A6, in Orientals has been shown to correlate with a 12 kb Bgl II fragment hybridizing with a C4 probe. It is likely that the HLA-B17 C4A6 B1 BfS DR7 supratype marks a highly conserved MHC chromosomal segment.
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PMID:Class III gene rearrangements in Thai/Chinese supratypes containing null or defective C4 alleles. 333 23

From the study of HLA, A, B, C, DR, Bf and C4A, C4B alleles in 287 insulin-dependent diabetes mellitus patients and 108 controls, comparisons were made between 424 diabetic and 216 normal extended haplotypes. In the "cis" situation (haplotype), the highest relative risks (RR) for IDDM were borne by multiloci allelic associations, mainly DR/complement alleles, rather than by DR3 or DR4 considered alone. Susceptibility was strongly associated with two extended haplotypes (Aw30, Cw5, B18, C4BQ0, C4A3, BfF1, DR3 and A2, Cw3, B15, C4Bx, C4A3, BfS, DR4) or their smaller segments. Two haplotypes, S31 associated with DR2 or DR5 and F31 associated with DRw6 or DR7 had a protective effect. In the "trans" situation (opposite haplotype) the large excess of DR3/DR4 heterozygotes was not the only distortion observed. An excess of DR1 (57%) and of C4BQ0 (40%) was noted among non DR3, non DR4 haplotypes in diabetics compared to normal individuals (26% and 23%, respectively, P less than 0.01, 0.05). Homozygotes for DR3 or DR4 were not increased, and other homozygotes were decreased compared to controls. The protective antigens HLA DR2, DR5 and DR7 seemed not to be distributed randomly: their putative protective effect was not observed in the case of combination with DR1 or a B18, DR3 haplotype. DR2 was never found homozygous or combined with DR5. These results suggest that susceptibility to IDDM is generated by both cis and trans interactions between genes or gene products of the HLA region.
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PMID:Study of cis and trans interactions between extended HLA-haplotypes in insulin-dependent diabetes. 340 91

In 6 type 1 (insulin-dependent) diabetics, treated with insulin since the age of 2 to 35 years (mean 12), coeliac disease was diagnosed between the 10 th and 73 th years of age (mean 26). Five were of North African origin. Digestive symptoms and severe malnutrition were present in all of them, associated, in the two younger, with a major growth retardation and, in one, multiple pathologic fractures. Biopsy of the small intestine demonstrated, in all, total or subtotal villous atrophy. The metabolic control of diabetes was poor, with frequent hypoglycaemic attacks, induced by minute insulin doses. Severe chronic complications of diabetes were detectable in all of them. Plasma anti-reticulin antibodies were present, at high titer before starting the gluten-free diet, declining slowly after starting this diet, and negative in the patients who followed this diet. Among the genetic markers (which were determined in 4), HLA A1 was present in 4, B8 and DR3 in 3 and DR4 in 3. The DR7 was not detected. The gluten-free diet, memorized by the patients by the use of simple rules, improved the digestive symptoms, and insulin doses could then be increased. The overall prognosis remained poor, due to diabetic complications and sociologic desinsertion. Coeliac disease occurs in 1 to 2% of type 1 diabetics and 4-6% of the coeliac patients are diabetics. Diabetic subjects from North Africa are at high risk of this association. Misdiagnosis of the coeliac disease compromises the metabolic control and nutritional state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Adult celiac disease and type 1 diabetes: a severe and sometimes unknown genetic association]. 342 65

The inherited susceptibility to autoimmune Addison's disease was found to be strongly associated with human leukocyte antigens (HLA)-DR3 and DR4 alleles. In a study of 45 white patients from the United States with the disease, the relative risks (the number of times that an individual is at risk for Addison's disease if they had a marker, compared to those without such marker) were found to be 6.0, 4.6, and 26.5 for the DR3 allele, the DR4 allele, and for DR3/DR4 heterozygotes, respectively. Frequencies of DR2, DR5, and DR7 in the patients with Addison's disease were significantly decreased in comparison to 265 individuals in the control population. These HLA-DR frequencies in patients with Addison's disease were similar to those for 723 patients with insulin-dependent diabetes (IDD). However, the above HLA-DR associations persisted even when only data from the 37 patients with Addison's disease who did not have IDD were considered. Adrenocortical autoantibodies in 23 patients with IDD who did not have Addison's disease were equally frequent among those with DR4 and DR3 alleles. In contrast, HLA-DR frequencies in 17 patients with type I autoimmune polyglandular syndrome (chronic mucocutaneous moniliasis, hypoparathyroidism, Addison's disease, etc.) were not different from control. We conclude that genetic susceptibility to autoimmune Addison's disease may involve the same HLA-associated genetic determinants as IDD, except when Addison's disease occurs as part of type I autoimmune polyglandular syndrome.
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PMID:Inherited susceptibility to autoimmune Addison's disease is linked to human leukocyte antigens-DR3 and/or DR4, except when associated with type I autoimmune polyglandular syndrome. 348 49

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

A child developed steroid-responsive nephrotic syndrome at the age of 3 years. 6 years later, he developed insulin-dependent diabetes mellitus. At this time renal biopsy disclosed minimal-change disease. After multiple relapses requiring cyclophosphamide or repeated courses of steroid therapy, a second renal biopsy, 5 years after the first, revealed early diabetic changes with associated exudative lesions. The nephrotic syndrome remains responsive to steroids and cyclophosphamide, and the patient maintains an increased glomerular filtration rate and normal blood pressure 3.5 years afterwards. His HLA typing showed DR4 and DR7. Since DR4 and DR7 are associated with diabetes and minimal-change disease, respectively, we speculate that he could carry the genetic predisposition for the development of both diseases.
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PMID:Steroid-responsive relapsing nephrotic syndrome associated with early diabetic glomerulopathy in a child. 360 Sep 16


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