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)

The levels of gamma aminobutyric acid decreased, while glutamic acid and aspartic acid levels increased in the forebrain, and decreased in the mid and hind brain regions of frog, Rana cyanophlictis during alloxan diabetes. Since glutamic acid and GABA are intimately involved in the central nervous system (CNS) functions, the alterations occurring in their levels during alloxan diabetes may be significant in bringing about a correlation between the diabetic state and the altered functional dynamics of the CNS.
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PMID:Neurochemical correlates of alloxan diabetes: gamma amino butyric acid of amphibian brain. 89 69

The AA. have examined 9 cases of normal pregnancy, 5 cases of E.P.H. gestosis and 5 cases of diabetes mellitus, for which cases caesarean section had been planed, determining the aminogram of the amniotic fluid, of the mother's venous plasma and of the umbilical venous plasma; the 3 samples were performed about contemporaneously. Both in the normal pregnancies and in those complicated by E.P.H. gestosis and by diabetes mellitus, the concentration of amino acids was higher in the umbilical venous plasma than in that of the mother and higher in the latter than in the amniotic fluid, with the exception of glycine, taurine, glutammic acid and aspartic acid in the normal pregnancies, of taurine in the gestosic pregnancies, of taurine, citrulline, glutammic and aspartic acid in the diabetic pregnancies.
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PMID:[Maternal and foetal aminoacidaemia and amino acids contents of amniotic fluid in normal, gestosic and diabetic pregnancy (author's transl)]. 122 66

Insulin-dependent diabetic and control subjects of Japanese origin were HLA-DRB1, -DQB1, and -DQA1 typed using restriction fragment length polymorphism analysis and sequence-specific oligonucleotide gene probing. The DQA1 allele DQA1*0301 was positively associated with the disease [48/52 (92%) diabetic patients versus 44/64 (69%) control subjects, Pc less than 0.03, RR = 4.97]. Alleles of the DRB1 and DQB1 genes showed no significant association with the disease. The frequency of DQB1 genotypes encoding the amino acid aspartic acid at position 57 of the DQ beta chain did not differ significantly between subjects with insulin-dependent diabetes mellitus (IDDM) and controls. These findings suggest that a susceptibility allele for IDDM in the Japanese is more closely associated with the DQA1 gene than the DQB1 gene.
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PMID:An investigation of Japanese subjects maps susceptibility to type 1 (insulin-dependent) diabetes mellitus close to the DQA1 gene. 134 65

In Caucasians the predisposition to Type 1 (insulin-dependent) diabetes mellitus has been shown to associate with HLA-DR3,DQw2 and DR4,DQw8 and with the presence of amino acids other than aspartic acid at position 57 on the HLA-DQ beta chain. In Finland the haplotype-specific absolute risk for developing Type 1 diabetes differs between various DR3 and DR4 positive haplotypes. The aim of our present analysis was to find out whether this variation is attributable to polymorphism at the DQ locus. As part of a nationwide prospective study including 757 serologically HLA genotyped families, we determined HLA-DQ alpha and DQ beta restriction fragment polymorphisms in 17 selected families with important susceptibility haplotypes. Additionally, the DQA1 alleles were determined from 19 haplotypes using sequence-specific oligonucleotide probes, and the DQB1 second exon was sequenced from nine haplotypes. The DR3 as well as DR4 positive haplotypes frequently found in Type 1 diabetic patients showed no variation at the HLA-DQ locus, and they were DQw2 and DQw8, respectively. The absolute risk for Type 1 diabetes for DR4,DQw8 positive haplotypes A2,Cw4,Bw35,DR4 A3,Cw3,Bw62,DR4, A24,Cw7,Bw39,DR4, A2,Cw3,Bw62, DR4, and A2,Cw1,Bw56,DR4 was 35/100,000, 130/100,000, 166/100,000, 196/100,000, and 218/100,000, respectively. The absolute risks for DR3,DQw2 positive haplotypes A1, Cw7,B8,DR3 and A2,Cw7,B8,DR3 were 68/100,000 and 103/100,000, respectively. These results provide further evidence that not only the polymorphism at the DQ locus but also other genes of the haplotypes contribute to susceptibility to Type 1 diabetes.
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PMID:HLA haplotypes in type 1 (insulin-dependent) diabetes mellitus: molecular analysis of the HLA-DQ locus. The DIME Study Group. 134 11

HLA-DRB, -DQA and -DQB genes were studied in ten South Indian malnutrition-related diabetic patients, ten Type 1 (insulin-dependent) diabetic patients and 45 control subjects, by TaqI restriction fragment length polymorphism analysis. The DR7,DQw9 haplotype was found to be frequent in patients with malnutrition-related diabetes (p less than 0.01). The DRw17,DQw2 haplotype was overrepresented in the patients with Type 1 diabetes compared to control subjects (p less than 0.05). In vitro amplification of the polymorphic second exon of DQB genes by the polymerase chain reaction technique was performed on DNA from 10 malnutrition-related diabetic patients, 10 Type 1 diabetic patients and 13 control subjects, as they belong to a new population. Hybridization with sequence-specific oligonucleotide probes for DQB1 alleles showed homozygosity of aspartic acid at position 57 in 7 of 10 malnutrition-related diabetic patients compared to 2 of 10 Type 1 diabetic (p less than 0.05) and 15 of 45 control subjects (p less than 0.05). Homozygosity of non-aspartic acid at position 57 was present in 7 of 10 Type 1 diabetic compared to 0 of 10 malnutrition-related diabetic patients (p less than 0.005) and 3 of 45 control subjects (p less than 0.05). This study has confirmed the association of DQB1 57 non-asp in South Indians with Type 1 diabetes. In addition, our data clearly show that the genetic background of malnutrition-related diabetes mellitus is different from that of Type 1 diabetes.
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PMID:Different genetic backgrounds for malnutrition-related diabetes and type 1 (insulin-dependent) diabetes mellitus in south Indians. 134 12

In this study we report, for the first time, the molecular analysis of HLA-DR and DQ gene frequencies in a large cohort of well-characterized type 1 (insulin-dependent) diabetes mellitus (IDDM) patients (n = 72), and ethnically matched controls (n = 59) collected in sub-Saharan Africa. High molecular mass DNA was prepared and analysed in Southern blots and by oligonucleotide typing. We have shown a strong positive association between IDDM and the Asp 57- DQB1 allele *0201 (DQw2). A rare DR4, DQw2 haplotype was also identified at high frequency in the IDDM cohort. We can now confirm that the association between Asp 57- DQB1 alleles and IDDM, previously reported in ethnically diverse cohorts collected in Western Europe, North America, and South Asia, is also present in an IDDM cohort collected in Africa.
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PMID:Identification of genetic susceptibility loci for insulin-dependent diabetes in Sudan. 135 6

The question of HLA susceptibility to Type 1 (insulin-dependent) diabetes mellitus remains unresolved. In the present study, 127 diabetic patients and 177 unrelated control subjects have been analysed for their class I and class II serological antigens, class II (DR, DQ) DNA restriction fragment length polymorphisms and DQA1 and B1 exon-2 nucleotide sequences and their corresponding amino acid residues. By using the aetiologic fraction (delta) as an almost absolute measure of the strongest linkage disequilibrium of an HLA marker to the putative Type 1 diabetes susceptibility locus, it has been found that the strength of association of the HLA markers may be quantified as follows: DR4 less than DR3 less than DR3 or DR4 less than non-Aspartate 57 beta DQ and Arginine 52 alpha DQ less than Arginine 52 alpha DQ. Thus, molecular HLA-DQ markers appear to be more accurate as susceptibility markers than the classic serologically defined ones (DR3 and DR4); however, any effect of DQ markers disappears when non-DR3/DR4 individuals are considered, suggesting that DR factors (or others in between DQ and DR) are also important. In addition, a dominant non-Aspartate 57 beta DQ susceptibility theory does not hold (but a recessive one does) in our diabetic population (probably due to the high frequency of the protective DR7-non-Aspartate 57 beta DQ haplotypes); Arginine 52 alpha DQ is the best single HLA marker found in our population, both as a recessive or as a dominant one. Also there are 13 patients in our sample who bear neither Arginine 52 alpha DQ nor non-Aspartate 57 beta DQ susceptibility factors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison between HLA-DRB and DQ DNA sequences and classic serological markers as type 1 (insulin-dependent) diabetes mellitus predictive risk markers in the Spanish population. 135 47

DNA sequence analysis of class II HLA from Caucasian and black patients with type 1 (insulin-dependent) diabetes mellitus has suggested that aspartic acid at position 57 (Asp 57) of the DQ beta chain provides protection against insulin-dependent diabetes mellitus (IDDM). In contrast, most Japanese patients with IDDM have Asp 57-positive alleles. To determine the reason for the differences and to localize the HLA-linked diabetogenic gene in Japanese, we studied the DQA1 and DQB1 genes of Japanese patients with IDDM and control subjects by the polymerase chain reaction in combination with restriction fragment length polymorphism analysis. Associations of DQA1*0301 and DQB1*0303 with IDDM were observed. DQA1*01 was associated negatively with IDDM. The HLA-DR9 haplotype, which is associated positively with IDDM in Japanese, was associated with DQA1*0301 and DQB1*0303, indicating that the Japanese DR9 haplotype is the same as that in caucasians but different from that in blacks. Of the loci on Japanese DR9 haplotypes, the DQA1*0301 allele showed the highest association with IDDM. DQB1*0303 was also positively associated with IDDM. Since DQB1*0303 is identical to DQB1*0302 except that it contains Asp 57, the data suggests that an Asp 57-positive allele confers susceptibility to IDDM when the whole molecule of the DQ beta chain is similar to other susceptible DQ beta chains. DQA1*0301 appears to be a marker of IDDM in all these populations: Japanese, caucasian, and black.
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PMID:Analysis by the polymerase chain reaction of histocompatibility leucocyte antigen-DR9-linked susceptibility to insulin-dependent diabetes mellitus. 135 11

Major determinants of susceptibility to Type 1 (insulin-dependent) diabetes (IDDM) have been mapped to the HLA complex, near to or identical with genes encoding class II molecules. The association of IDDM with HLA-DR3 and/or DR4 antigens and the highest risk for DR3/4 heterozygotes suggest a synergistic effect of the two haplotypes. The characterization at the molecular level of the class II region has provided evidence that DQ rather than DR determinants may primarily influence the disease. In caucasians the susceptibility strongly correlates with the absence of aspartic acid at position 57 on the DQ beta chain and/or the presence of arginine at position 52 on the DQ alpha chain. The formation of a putative DQ susceptibility molecule (DQ alpha Arg52+, DQ beta Asp57-) accounts best for the disease associations when trans-complementation between alpha and beta chains encoded by different haplotypes is postulated to explain the excess of heterozygotes. Observations in other populations and in animal models indicate, however, that other residues on DQ alpha and beta chains, other class II (DR beta) molecules and non-HLA linked genes also contribute to the susceptibility. The mechanism(s) by which susceptibility determinants influence IDDM is not known. It is probably in relation with the role of class II molecules in the antigen presentation to T lymphocytes.
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PMID:[The role of the HLA system in the genetics of Type I diabetes mellitus]. 145 12

Some insulin-dependent diabetic patients present with auto-immune diseases involving extra pancreatic tissues (type 1b diabetes mellitus). The genetic specificity of this syndrome, as opposed to insulin dependent diabetes mellitus (IDDM) free of such associations (Type 1a IDDM) is not clearly established. We have analyzed the HLA-DQB1 and DQA1, loci, after PCR amplification of genomic DNA, in 44 Type 1b IDDM patients, 78 Type 1a IDDM patients and 105 control subjects. No essential difference in HLA-DQ profiles appeared between Type 1b and Type 1a IDDM patients. Both diabetic groups displayed a significant enrichment in DQB1 alleles negative for aspartate at position 57 (Type 1b: 83%; Type 1a: 89%; controls 48%; p < 0.001 vs both patient groups) and in DQB1 Asp 57 negative homozygosity: 71% of Type 1b; 80% of Type 1a; 25% of controls (p < 0.01). This enrichment in DQB1 Asp 57 negative alleles was accounted for by DQB1* 0201 in the Type 1b group, and by DQB1 % 0201 and 0302 in the Type 1a patients. Conversely, alleles DQB1* 0602 and 0301 (DQB1 Asp 57 positive) were protective. Both diabetic groups also displayed a significant enrichment in DQA1 alleles positives for arginine at position 52 (65% of Type 1b; 76% of Type 1a; 50% of control subjects; p < 0.01 and 0.001, respectively, vs controls), and in DQA1 Arg 52 positive homozygotes (48% of Type 1b, 58% of Type 1a, 22% of control subjects; p < 0.01). All differences between diabetic groups and the control group were more pronounced in the case of Type 1a than of Type 1b patients. The HLA-DQ genes shared by Type 1a and Type 1b patients must therefore be closely associated with islet autoimmunity. Genetic differences between Type 1a and Type 1b syndromes, if any, must be investigated in other MHC and non-MHC regions of the genome.
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PMID:Similarity of HLA-DQ profiles in adult-onset type 1 insulin-dependent diabetic patients with and without extra-pancreatic auto-immune disease. 145 19


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