Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred and thirty-six Finnish patients with insulin-dependent (type I) diabetes mellitus were investigated for the HLA-A, B, D and DR antigens as well as the Bf and C4 allotypes. The statistically significant increase in the frequencies of HLA-A9, B8, B15, Dw3, Dw4, DR3, DR4, C4A0 and C4B3 was observed when compared with the healthy controls. About 79% of the patients had HLA-DR4, and 53% had HLA-DR3 antigens. A rare C4 allele C4B3 was found in 21% of the patients, whereas only in 2% among the controls (relative risk 16.35). The etiological fraction (EF) values indicated that HLA D/DR alleles were the best markers for IDDM, the observed EF for HLA-DR4 in diabetes was as high as 0.70. Examination of HLA, Bf and C4 phenotypes suggested that at least two supratypes "B15 BfS C4A3B3 D(R)4" and "B8 BfS C4A0B1 D(R)3" were markers for the susceptibility to type I diabetes, one third of our patients had either of these supratypes. The protective role of DR2 and Dw2 antigens was also confirmed: no HLA-Dw2 positive patients and only one with HLA-DR2 was found.
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PMID:HLA antigens and complotypes in insulin-dependent diabetes mellitus. 346 Feb 20

Duration of disease is the major susceptibility factor for microangiopathy. Microangiopathy does not occur without the metabolic abnormality of diabetes and there is much circumstantial evidence to implicate poor diabetic control in its pathogenesis. The rate of development and severity of complications, however, are variable even in patients with apparently similar control and about 25% of diabetics will never develop clinical evidence of microangiopathy. Studies of identical twins suggest a genetic component in the pathogenesis of retinopathy in NIDDM, and less so in IDDM, but increased capillary basement membrane thickness does not occur in the non-diabetic identical co-twins of insulin dependent diabetics. There may also be genetic heterogeneity not only of diabetes, but also of its complications, although for a given type of diabetes the prevalence of microangiopathy is often very similar in different racial groups. Associations between several different HLA molecules (particularly DR4) and microangiopathy in IDDM have been reported but not consistently confirmed. Recently the finding of an increased frequency of the B3 allotype of the fourth component of complement C4B3 in subjects with retinopathy has suggested that there is an HLA linked association. Both complement and the immunoglobulins are concerned with humoral immunity and the report of an association between a phenotype of the IgG heavy chain markers on chromosome 14 and retinopathy is of particular interest. These associations appear to be additive but independent. These reports need confirmation but provide the best evidence we have for an immunogenetic component (HLA and non-HLA linked) of the aetiology of microangiopathy, at least in IDDM. The studies of identical twins, HLA and Gm associations provide good evidence that genetic factors are involved in susceptibility to microangiopathy, at least in some diabetics, although the most relevant genes may not have been identified. Searches for better genetic markers must continue in order to identify those patients at increased risk of developing microangiopathy.
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PMID:The genetics of diabetic complications. 353 96

About a quarter of insulin dependent diabetics have low concentrations of the fourth component of complement (C4), and a low concentration of C4 is associated with diabetic microangiopathy. The variability of the expression of the C4 gene was compared in insulin dependent diabetics with and without microangiopathy and controls. Of the two genes coding for C4, the A gene (C4A) was not expressed--that is, C4A null--in 16 (13%) of the 126 insulin dependent diabetics compared with none of the 93 controls (p less than 0.001), and all these 16 subjects had low concentrations of C4. Lack of expression of the other C4 gene (C4B) was not associated with insulin dependent diabetes, but a rare variant, C4B3, was significantly increased in the diabetics (21/126; 17%) compared with the controls (none) (p less than 0.001). The prevalence of C4B3 was also increased in the diabetics with complications when compared with those without (14/50 (28%) v 7/76 (9%), p less than 0.01). Low plasma C4 concentrations in insulin dependent diabetics are at least partly due to variation in the expression of the C4 gene. The association of the rare C4B3 variant with microangiopathy suggests a genetic component of its aetiology.
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PMID:Relation of gene expression (allotypes) of the fourth component of complement to insulin dependent diabetes and its microangiopathic complications. 392 68

Subtypes of HLA-DR4 are associated with susceptibility or protection against type 1 diabetes (T1DM). We addressed whether this reflects linkage disequilibrium with the true susceptibility locus by studying broader MHC haplotypes marked by alleles of HLA-B, IKBL (adjacent to TNFA) and complement C4. The study used a largely Caucasian cohort from Western Australia. HLA-DRB1*0401 and HLA-DRB1*0405 marked susceptibility to T1DM. In Caucasians, DRB1*0401 occurs predominantly in the 44.1 ancestral haplotype (AH; HLA-A2,B44, DRB1*0401,DQB1*0301) and the 62.1AH (HLA-A2,B15(62),DRB1*0401,DQB1*0302). HLA-B15 marked susceptibility and HLA-B44 marked with resistance to T1DM in patients and controls preselected for HLA-DRB1*0401. A gene between TNFA and HLA-B on the 8.1AH (HLA-A1,B8,;DR3,DQ2) modifies the effects of the class II alleles. Here, alleles characteristic of the 62.1AH (C4B3, IKBL+446*T and HLA-A2,B15) were screened in donors preselected for HLA-DRB1*0401. C4B3 was associated with diabetes, consistent with a diabetes gene telomeric of MHC class II. However, increases in carriage of IKBL+446*T and HLA-A2,B15 were marginal, as too few control subjects were available with the diabetogenic alleles. However, with these tools, selection of HLA-DRB1*0401, DQB1*0302 donors who are positive and negative for C4B3 will allow bidirectional mapping of diabetes genes in the central MHC.
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PMID:Does a central MHC gene in linkage disequilibrium with HLA-DRB1*0401 affect susceptibility to type 1 diabetes? 1585 1