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

Fifty-seven Thai IDDM patients were studied for HLA class I by LCT and HLA class II by LCT and PCR-RFLP. It was found that DRB1*0301, DR3, DQB1*0201, DRB3*0202, DQA1*0501 and DQ2 were significantly increased with R.R. = 10.0, 6.6, 4.2, 3.7, 3.5 and 3.2 and Pc < 0.005, 0.001, 0.01, 0.005, 0.01 and 0.005, respectively. In contrast, DQA1*0101, DRB3*0301, DR5 and DQ1 were significantly decreased with R.R. = 0.2, 0.2, 0.3 and 0.5 and Pc < 0.01, 0.05, 0.01 and 0.05, respectively. The primary factor for IDDM susceptibility is probably DRB1. The homozygous Asp57/Asp57 DQB1 genotype appears to determine resistance to IDDM while Arg52-DQA1, non-Asp57-DQB1 haplotype confers susceptibility to IDDM. The common haplotypes in Thai IDDM cases were DRB1*0301, DRB3*0202, DQA1*0501, DQB1*0201, DPB1*0401 and DRB1*0405, DQA1*0301, DQB1*0402 (or 0401 or 0302), DPB1*0401 (or 0301 or 1501). The less common haplotypes were DRB1*0406, DQA1*0301, DPB1*0302, DPB1*0501 and DRB1*1202, DRB1*0301, DQA1*0601, DQB1*0301, DPB1*0501. DR3 was increased in both gender groups with early onset (< 10 years) regardless of a family history of DM. However, DR3/DR4 genotype was increased only in female patients with a family history of DM and early onset. In conclusion, DRB1, DRB3, DQA1 and DQB1, but not DPB1 are involved in the occurrence of IDDM. The cooperation of HLA class II and X-chromosome may contribute to the development of IDDM in addition to other factors such as other genetic (chromosomes 11, 19, 14, 7), immunologic and environmental factors which require further study.
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PMID:HLA class II polymorphism in Thai insulin-dependent diabetes mellitus. 766 Mar 88

Although one of the major genes which cause type 1 (insulin-dependent) diabetes mellitus is located in the class II HLA region in humans, its precise location is still unknown. In order to investigate whether TAP (Transporter associated with Antigen Processing) and LMP (Low Molecular Weight Polypeptide) genes, which are located in the class II HLA region, are HLA-linked diabetogenic genes, the association of TAP1, TAP2 and LMP2 genes with type 1 diabetes was analyzed in the Japanese population. No difference in allele frequencies of these genes was detected between diabetic patients and control subjects. On the other hand, DQA1 and DQB1 genes showed significant association with type 1 diabetes. These data suggest that the diabetogenic gene in the class II HLA region may be located near the DQA1 and DQB1 loci, rather than the TAP and LMP loci.
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PMID:Absence of association of TAP and LMP genes with type 1 (insulin-dependent) diabetes mellitus. 791 50

The HLA-DQA1 and DQB1 genes have recently been recognized to be strong genetic markers of susceptibility to type 1 (insulin-dependent) diabetes mellitus. The Arg52 DQA1 and non-Asp57 DQB1 alleles of these genes correlate with the disease predisposition and the Asp57 DQB1 and non-Arg52 DQA1 alleles with disease protection. We investigated 113 patients with type 1 diabetes and 121 healthy subjects from the Russian population of Moscow using DNA amplification and dot-blot hybridization with sequence-specific oligonucleotides (SSO). Using conventional statistical methods we confirmed previous observations indicating the important role of the above-mentioned amino acid residues in susceptibility and resistance to type 1 diabetes. Relative risk values for all alleles and absolute risk for carriers of most predisposing allele combinations were calculated. The absolute risk for carriers of DQA1 and DQB1 gene alleles allowing for the formation of four possible 'diabetogenic' heterodimers on the surface of immunocompetent cells, regardless of the type of coding (cis or trans), was 2.54%, which is 13 times greater than the background risk for the Russian population--0.2% up to 30 years of age.
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PMID:Frequency analysis of HLA-DQA1 and HLA-DQB1 gene alleles and susceptibility to type 1 diabetes mellitus in Russian patients. 794 27

Trans-racial analysis of disease association has improved mapping of MHC-linked susceptibility to insulin dependent diabetes mellitus (IDDM). In this study, the contribution of the HLA class II DQA1 and DQB1 genes was investigated. Nine DQA1 and 10 DQB1 sequence-specific oligonucleotide gene probing in 49 IDDM and 48 control subjects from Beijing showed that DQA1-A4 alleles was positively associated with the disease (RR = 11.7, Pc < 0.02) as was the Asp57 negative homozygotes of DQB1 gene (P < 0.01, RR = 5.3), and that Asp57 positive homozygote of DQB1 gene conferred protection against IDDM (P < 0.025, RR = 0.38). Compared with trans-racial study, the decrease of Asp57 negative homozygote frequence and increase of Asp57 positive homozygote frequence in Chinese population may contribute to the low incidence of IDDM.
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PMID:[HLA-DQ gene and susceptibility of insulin dependent diabetes mellitus in Chinese population]. 798 15

We examined the prevalence of HLA-DRB1, DQB1, DQA1 and TAP2 genes in children with insulin-dependent diabetes mellitus (type 1 diabetes). These HLA and TAP2 alleles were identified by dot-blot analysis of polymerase chain reaction (PCR)-amplified genomic DNA with sequence-specific oligonucleotide probes. The results show that those DQB1 alleles, which carry non-aspartic acid at position 57, in conjunction with DQA1 alleles carrying arginine at position 52, are strongly associated with susceptibility to type 1 diabetes. The prevalence of the TAP2* 0201 allele in diabetic patients was significantly lower than that in normal controls. Analysis of the data suggests that DQ alleles have the primary association with type 1 diabetes and that the association of TAP2 alleles with the disease is secondary.
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PMID:HLA-DQ and TAP2 genes in patients with insulin-dependent diabetes mellitus. 800 38

Insulin-dependent diabetes mellitus (IDDM) is strongly associated with the presence of arginine in position 52 of the DQ alpha chain and absence of aspartic acid in position 57 of the DQ beta chain in Caucasians. With the aim of confirming this association in Chinese, extensive oligonucleotide dot blot hybridization of PCR-amplified DQA1 and DQB1 genes was studied using samples from 48 IDDM patients and 46 healthy nondiabetic control subjects. Three major findings emerged from our analysis. 1) DQ alpha 52-Arg and DQ beta 57-non-Asp are strongly associated with IDDM susceptibility as compared with controls (P < 0.001 and 0.005, respectively). 2) DQ beta 57-non-Asp homozygous (NA/NA) is associated with increased susceptibility to IDDM (22.9% vs 2.2% in controls, P < 0.01). DQ beta 57-Asp homozygous (A/A) is associated with protection against IDDM (14.6% vs 47.8% in controls, P < 0.01). 3) In this study, about 14.6% of IDDM patients were homozygous for DQ beta 57-Asp, compared with 0% of American patients. Only 22.9% were homozygous for DQ beta 57-Asp, compared with 96% of American diabetic subjects in a previous study. Thus it is unlikely that the DQ beta 57 amino acid has a major effect on IDDM susceptibility in Chinese.
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PMID:HLA-DQA and DQB alleles contribute to susceptibility to insulin-dependent diabetes mellitus. 803 70

The transporter associated with antigen processing (TAP) encoded in the major histocompatibility complex (MHC) class II region is a molecule required for endogenous antigen processing. We have typed TAP polymorphism in 95 Japanese patients with insulin-dependent diabetes mellitus (DDM) and 75 normal controls. Amino acid substitutions at positions 333 and 637 of TAP1 and at positions 379, 665, and 687 of TAP2 were typed by the polymerase chain reaction (PCR)-sequence-specific oligonucleotide method. In addition, DNA typing of human leukocyte antigen (HLA)-DQA1 and -DQB1 loci was performed by the PCR-restriction fragment length polymorphism method. There was no significant difference between IDDM patients and normal controls in the frequencies of TAP1 and TAP2 alleles. On the contrary, the HLA-DQ locus showed a strong association with IDDM in the same series of subjects. The frequencies of HLA-DQA1*0301 and -DQB1*0401 were increased significantly and those of HLA-DQA1*0103, -DQB1*0501, -DQB1*0601 and -DQB1*0602 were decreased significantly in Japanese IDDM patients compared with normal controls. Positive linkage disequilibrium was observed between HLA-DQB1*0303 and TAP2C and between HLA-DQB1*0401 and TAP2B. Negative linkage disequilibrium was observed between HLA-DQA1*0103 and TAP2A. Even when subjects with HLA-DQA1*0103, -DQA1*0301, -DQB1*0302, -DQB1*0303, and -DQB1*0401 were considered separately, no significant differences was found in the distribution of TAP1 and TAP2 alleles between IDDM patients and normal controls. We conclude that it is not TAP but HLA-DQ that exhibits a primary association with Japanese IDDM.
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PMID:Lack of association of the transporter associated with antigen processing with Japanese insulin-dependent diabetes mellitus. 805 40

We examined HLA Class II antigens in 116 Japanese IDDM patients [84 typical IDDM (T-IDD); 32 slowly progressive IDDM (S-IDD)] by the hybridization protection assay (HPA) which is a novel HLA typing method based on hybridization of acridinium-ester-labeled DNA probes to amplified DNA. We detected HLA-DRB1, -DQA1 and -DQB1 genes by this method which is capable of analyzing over 50 samples within 4 h with high sensitivity. Positive associations were found in DRB1*0405, DRB1*0802, DRB1*0901, DQA1*0301, DQB1*0303 and DQB1*0401, negative correlations in DRB1*0403, DR2, DR12, DRB1*0801 or 03, DQA1*0101 or 02, DQA1*0501, DQB1*0301 and DQB1*0602 alleles. The absence of aspartic acid (Asp) at position 57 of the DRB1 chain and the presence of arginine (Arg) at position 52 of the DQA1 chain correlated positively with both types of IDDM. There were no significant differences in HLA between T-IDD and S-IDD. These results suggest that the absence of Asp at position 57 of the DRB1 chain and the presence of Arg at position 52 of the DQA1 chain are significant Japanese IDDM patients and that DRB1*0802, in which the amino acid at position 57 is aspartic acid, may play a role in the pathogenesis of IDDM. Also, T-IDD and S-IDD have common bases in the HLA gene.
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PMID:Analysis of MHC class II antigens in Japanese IDDM by a novel HLA-typing method, hybridization protection assay. 807 Mar 5

The particular histocompatability antigen (HLA) gene(s) that may confer systemic lupus erythematosus (SLE) susceptibility remains unknown. In the present study, 58 unrelated patients and 69 controls have been analyzed for their class I and class II serologic antigens, class II (DR and DQ) DNA restriction fragment length polymorphism, their deduced DQA1 and B1 exon 2 nucleotide sequences and their corresponding amino acid residues. By using the etiologic fraction (delta) as an almost absolute measure of the strongest linkage disequilibrium of an HLA marker to the putative SLE susceptibility locus, it has been found that the strength of association of the HLA marker may be quantified as follows: DQA1*0501 (associated to DR3) or DQB1*0201 (associated to DR3) > non Asp 57 beta DQ/Arg 52 alpha DQ > DR3 > non Asp 57 beta DQ. Thus, molecular HLA DQ markers tend to be more accurate as susceptibility markers than the classical serologic markers (DR3). However, dominant or recessive non Asp 57 beta DQ susceptibility theories, as previously postulated for insulin-dependent diabetes mellitus, do not hold in our SLE nephritic population; indeed, three patients bear neither Arg 52 alpha DQ nor Asp 57 beta DQ suscepibility factors. On the other hand, nonsusceptibility factors are included in our population in the A30B18CF130-DR3DQ2(Dw25) haplotype and not in A1B8CS01-DR3DQ2(Dw24); this distinctive association has also been recorded in type I diabetes mellitus and may reflect the existence of common pathogenic HLA-linked factors for both diseases only in the A30B18CF10DR3DQ2(Dw25) haplotype. Finally, the observed increase of deleted C4 genes (and not 'null' C4 proteins) in nephritic patients shows that C4 genes are disease markers, but probably without a pathogenic role.
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PMID:Differential contribution of C4 and HLA-DQ genes to systemic lupus erythematosus susceptibility. 810 32

The allelic constitution at HLA class II DRB1, DQB1, DQA1, and DPB1 loci of IDDM patients from Taiwan was compared with that of ethnically matched nondiabetic individuals by PCR-based DNA typing. Of the three haplotypes found to be positively associated with IDDM in Taiwan, two (DRB1*0301-DQA1*0501-DQB1*0201 and DR4-DQA1*0301-DQB1*0302) appear to be identical to the susceptible haplotypes in Caucasian and black populations, whereas the third haplotype (DR4-DQA1*0301-DQB1*04) has been reported to be positively associated with IDDM only in the Japanese population. The three haplotypes, DRB1*1502-DQA1*0102-DQB1*0601 and DRB1*1201 (or 1202)-DQA1*0501-DQB1*0301 and DRB1*0803-DQA1*0103-DQB1*0601, were negatively associated with IDDM in Taiwan; a protective effect of the last haplotype has not been reported previously. Neither DQ beta non-Asp-57 nor DQA1*0301 alone appears sufficient to account for the HLA-associated susceptibility to IDDM in Taiwan. Also, the DQ alpha beta heterodimer encoded by the alleles DQA1*0301/DQB1*0201, DQA1*0301/DQB1*0302, or DQA1*0501/DQB1*0201 does not explain the susceptibility of a larger fraction of the IDDM patients than the residue at position 57 of the DQ beta chain or DQA1*0301. Finally, the DRB1 alleles appear to affect IDDM susceptibility, although for most haplotypes the effect of individual loci cannot be assessed due to the linkage disequilibrium between the DQ and the DR region.
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PMID:Association of insulin-dependent diabetes mellitus in Taiwan with HLA class II DQB1 and DRB1 alleles. 810 65


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