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 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

HLA frequency distributions in Fiji Indians with non-insulin dependent diabetes were compared with those in control subjects with confirmed two-hour plasma glucose levels less than 7.8 mmol/L. Antigen frequencies at HLA-A and HLA-DR loci were similar in patients and controls. At HLA-B, there was a significant increase in Bw61 (Bw40.2) in diabetics, with a relative risk for this antigen of 4.8. Since a similar finding has been reported previously in South African Indians with Insulin-dependent diabetes, it is possible that wer have defined yet another genetically-distinct form of diabetes, especially prevalent in Indians. Alternatively, definition of new HLA alleles such as Bw61, a new subdivision of an established antigen, may reveal HLA associations with non-insulin dependent diabetes in European Caucasians also.
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PMID:HLA and non-insulin dependent diabetes in Fiji indians. 694 7

Cold-reacting serum lymphocytotoxic antibodies (LCAs) were measured in sera from 230 insulin-dependent juvenile-onset diabetes mellitus (IDDM) patients and from 116 control subjects. LCAs were present in only 4% of control sera compared with 19% in IDDM patients. The most significant determinant of LCAs was time since onset of diabetes; within the first 12 mo, 55% of IDDM sera had LCAs, compared with 25% after one year and 15% after five years of diabetes. LCAs were absent in sera from patients with IDDM for 10 yr or more. Genetic factors were also implicated in susceptibility toi occurrence of LCAs. HLA antigen B8 and B18 were associated with an increased risk for LCAs, whereas HLA-B7 was associated with a decreased risk. The relative risk for LCAs in patients positive for HLA-B8 but not B7 was 2.3, compared with 0.0 in HLA-B7/B8 heterozygotes. In contrast, B7 did not provide protection from LCAs in B18/B7 IDDM patients. Properdin factor B (Bf) alleles, which are in linkage disequilibrium with alleles of the HLA-B locus, were also associated with LCAs, IDDM patients with alleles BfS1 or BfF hd a prevalence of LCAs of 7%, significantly less than the 39% in Bf-F1S or -F1 patients. LCAs were not identical or closely correlated to pancreatic islet cell antibodies. Our findings indicate genetic heterogeneity in, yet, another autoimmune process in IDDM.
Diabetes 1981 Jan
PMID:Lymphocytotoxic antibodies and histocompatibility antigens in juvenile-onset diabetes mellitus. 701 2

In 129 patients with Type 1 (insulin-dependent) diabetes mellitus, 100 healthy control subjects and 91 non-diabetic first degree relatives of Type 1 patients, we investigated variation in serum IgA, IgG and IgM concentrations with sex and HLA-B phenotype. Two patients with onset before the age of 15 years were completely IgA-deficient. One additional patient was completely IgG-deficient. Excluding these three cases, diabetic patients had serum IgA and IgM concentrations comparable to control subjects. IgG levels of patients were, however, significantly lower than those of control subjects (11.66 versus 12.69 g/l, p = 0.003). Non-diabetic first degree relatives of patients had IgG levels intermediate between those of diabetic patients and control subjects. There was some indication that IgA concentrations were lower in the 53 patients with HLA-B8 (1.91 versus 2.21 g/l, p = 0.038). No association was found between IgM or IgG levels and HLA phenotypes.
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PMID:Immunoglobulin levels, immunodeficiency and HLA in type 1 (insulin-dependent) diabetes mellitus. 714 Nov 66

Diabetes is a heterogeneous disease, and its pathogenesis and etiology are still largely unknown. Recent studies have brought new knowledge showing that HLA antigens and diabetes mellitus are related. It has been found that the relative risk of juvenile onset diabetes requiring insulin treatment is greater for persons who are HLA-A1, A2, B8, BW15, BW40, CW3, DW3, DW4, DRW3 and DRW4 positive. The relative risk of the disease is additive in persons who have two of the above mentioned HLA-B alleles. Some HLA antigens (HLA-B7, DW2, DRW2, A11) are associated with a significantly lower risk of the disease and probably have a "protective" character. Maturity onset diabetes (MOD) and maturity onset diabetes not requiring insulin treatment (MODY) are not related to the HLA system. This means that MOD is completely distinct from JOD with different symptoms, course and etiopathogenesis.
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PMID:[The HLA system and diabetes mellitus]. 722 46

Diabetic nephropathy with renal failure is a major cause of death among juvenile diabetics. It is as yet unknown why some diabetics suffer from this serious renal complication while others do not, in spite of long duration of diabetes. For therapeutic reasons it is of the utmost importance to find out which patients are at risk long before the manifestation of renal insufficiency. Juvenile diabetics are know to have an increased frequency of some HLA antigens. The relationships between the HLA-A, HLA-B and HLA-C antigens and diabetic end-stage nephropathy were therefore evaluated in the present study. The study comprised 121 insulin-dependent diabetics with renal failure (mean age at onset of diabetes 13.4 leads to 7.6 (SD) years, mean pre-uraemic duration of diabetes 21.7 leads to 4.7 years), and 36 insulin-dependent diabetics (mean age at onset of diabetes 16.5 leads to 8.4 years) without renal failure despite long mean duration of diabetes (32.5 leads to 5.1 years). We found the expected significant increase in B8 and B15 and a decrease in B7 frequencies in the diabetics compared with the non-diabetic population, but no difference was found between uraemic and non-uraemic diabetics. Neither the early onset of diabetes nor the rapid appearance of renal failure was associated with any HLA frequency. The data therefore do not provide evidence of the involvement of B8 or B15 allele-associated mechanisms in the disease process leading to diabetic nephropathy with renal failure. There was a significant difference (p corrected less than 0.01) between the frequency of Bw22 in uraemic diabetics (14%) and that in non-diabetics (5%) while the frequency was near normal in non-uraemic diabetics. Further data are needed to confirm the possible association of Bw22 with diabetic nephropathy.
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PMID:HLA-antigen distribution in juvenile diabetics with end-stage nephropathy. 723 15

HLA-D specificities have been investigated in 58 classical Type 1 diabetics and 43 healthy subjects. Both groups were selected according to the HLA-B locus antigens which are known to have a significant positive or negative association with the disease. The results indicate that (1) the primary association of the disease is with HLA-DW3, (2) the increased frequency of DW4 in diabetics with rare exception is co-existent with the presence of DW3, (3) the low frequency of DW2 is secondary to the increase in DW3 and/or DW4, and is not consistent with a primary 'protective' role. It is suggested that these data support the hypothesis of interaction between HLA-linked genes operating by separate mechanisms to confer the susceptibility to young onset Type 1 diabetes (Type 1 A).
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PMID:Type 1 diabetes and the HLA-D locus. 736 63

We have used the novel strategy of overlapping yeast artificial chromosome (YAC) clones to localize a series of new transcripts within a 170 kb region of the human major histocompatibility complex (MHC), containing genes likely to be of importance for disease susceptibility. Using cloned genomic probes we have further localized these transcripts to a region 15 kilobases (kb) centromeric of HLA-B. In the liver there are at least four transcripts ranging in size between 7.5 kb and 3.4 kb, while in the lung two transcripts of 5.8 kb and 4.2 kb are detected. The possible implications of these transcripts for autoimmune disease are discussed, given that they are located in a region previously shown to be of importance for susceptibility to insulin-dependent diabetes mellitus and myasthenia gravis. Furthermore, we conclude that YACs as large as 360 kb are able to be used as probes to identify new transcripts and that the MHC region between HLA-B and BAT1 is the site of a large multiply spliced gene, provisionally designated PERB6.
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PMID:Large transcripts and sequence from a polymorphic 170 kb MHC region implicated in susceptibility to autoimmune disease. 769 83

In Finland the haplotype A2, Cw1, B56, DR4, DQ8 is the third most common haplotype in insulin-dependent diabetic (IDDM) patients and has the highest haplotype-specific absolute risk for IDDM. Cw1, B56, DR4, DQ8 haplotypes containing HLA-A alleles other than A2 are infrequent in the population and are not associated with IDDM. Comparison of the A2 and non-A2 haplotypes at the DNA level showed that they were identical at HLA-B, -DR, and -DQ loci. Evidence that class I alleles confer susceptibility to IDDM was obtained from the two HLA-C, -B, -DR and -DQ haplotypes most frequently found in IDDM patients in Finland. A24, A3 and A2 on the Cw3, B62, DR4, DQ8 haplotype, and A28, A2 and A1 on the Cw7, B8, DR3, DQ2 were all found to be associated with IDDM. In Finland these seven haplotypes, including A2, Cw1, B56, DR4, DQ8, account for 33% of diabetic haplotypes and 10.3% of non-diabetic haplotypes (p < 0.00001). The contribution of the class I region to IDDM susceptibility was also apparent in those IDDM patients lacking the disease-predisposing class II alleles. Significantly more non-DR3/non-DR4 IDDM patients (47 of 55) possessed two of the IDDM-associated HLA-A alleles compared to non-DR3/non-DR4 control subjects (40 of 58; p = 0.038). Moreover, IDDM patients confirmed by oligotyping as unable to form a 'diabetes-susceptibility' DQ heterodimer, tended to possess two diabetes-associated HLA-A alleles (12 of 13) compared to control subjects (12 of 20; p = 0.056).
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PMID:A gene in the HLA class I region contributes to susceptibility to IDDM in the Finnish population. Childhood Diabetes in Finland (DiMe) Study Group. 767 3

In the present study we characterized the frequencies of two polymorphisms within the MHC-linked heat shock protein (HSP) 70 genes in patients with insulin-dependent diabetes mellitus (IDDM) (n = 114) and healthy control individuals (n = 110). Significant differences in genotype and allelic frequencies were observed for both polymorphisms between randomly selected patients and controls. However, for the HSP70-2 polymorphisms this was solely due to linkage disequilibrium with DR3. The rate HSP70-Hom 2-allele was significantly more frequent in controls than in patients. It showed strong association with certain tumour necrosis factor (TNF) (class III) and HLA-B and -A (class I) alleles independent of HLA-DQ and -DR alleles. By typing 257 individuals from 55 IDDM multiple-case families two extended MHC-haplotypes, including class II-, TNF- and class I-markers, carrying the rare HSP70-Hom allele were defined. One was only transmitted to diabetic offspring, whereas the other was only transmitted to unaffected offspring. The functional implication of the polymorphism in the heat shock-inducible HSP70-2 gene was analysed by studying HSP70-2 mRNA expression after heat shock in peripheral blood mononuclear cells from individuals with different HSP70-2 genotypes. Preliminary data showed that individuals homozygous for the PstI 8.5-kb allele consistently had slightly lower expression than heterozygous and 9.0-kb homozygous individuals.
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PMID:Polymorphic analysis of the human MHC-linked heat shock protein 70 (HSP70-2) and HSP70-Hom genes in insulin-dependent diabetes mellitus (IDDM). 790 96


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