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 association of HLA-DRB1 and DQB1 genes with IDDM in Koreans was assessed using 115 IDDM patients and 140 nondiabetic controls. DQB1*0201 is the only DQB1 allele positively associated with IDDM while DQB*0602, *0601 and *0301 are negatively associated. Three DRB1 alleles (DRB1*0301, DRB1*0407 and DRB1*0901) are positively associated while four DR allele groups (DRB1*15, DRB1*12, DRB1*10 and DRB1*14) are negatively associated. However, Haplotype analyses indicated that DQB1*0302, DRB1*0405 and DRB1*0401 may confer susceptibility because the DRB1*0405-DQB*0302 and DRB1*0401-DQB1*0302 haplotypes are positively associated with the disease. The lack of association in Koreans with the DQB1*0302 allele, which appears predisposing in studies of non-Orientals, is due to its strong linkage disequilibrium (LD) with the protective DRB1*0403 and *0406 alleles, while the lack of association with DRB1*0405 is because of its strong LD with the protective DQB1*0401 allele. Nine DR/DQ genotypes confer significantly increased risk to IDDM. Seven of the nine genotypes (DR3/4s, DR1/4s, DR4s/13, DR4s/8, DR4s/7, DR9/13 and DR3/9) were also found to be at high risk to IDDM in other populations, while the two others (DR1/9 and DR9/9) are only found in Koreans. Surprisingly, DR4/4 homozygotes are not associated with high risk to IDDM in Koreans. This observation can be explained by the high frequency of protective DR4 subtypes and the protective DQ alleles (0301 and 0401) associated with the susceptible DR4 alleles. Our analyses indicate that the counterbalancing act between susceptible DRB1 and protective DQB1, and vice versa, that has already been observed in Chinese and Japanese, is the major factor responsible for the low incidence of diabetes in Koreans.
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PMID:Combinations of HLA DR and DQ molecules determine the susceptibility to insulin-dependent diabetes mellitus in Koreans. 983 Nov 35

A 61-year-old woman with a 2-year history of insulin-dependent diabetes mellitus (IDDM) developed nephrotic syndrome. Renal biopsy showed minimal-change nephrotic syndrome (MCNS), and no evidence of diabetic glomerulosclerosis. Although steroid therapy was initiated, plasma urea and creatinine rose and hemodialysis was required. After 4 weeks, she responded to steroids and her renal function returned to normal. MCNS, which is not associated with diabetic glomerulosclerosis, has rarely been seen in IDDM patients with nephrotic syndrome. Her human leukocyte antigen typing was A24, BW52, BW61, DR2 and DR9. This typing has been reported to be associated with both IDDM and renal disease.
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PMID:Minimal-change nephrotic syndrome and acute renal failure in a patient with aged onset insulin-dependent diabetes mellitus and autoimmune thyroiditis. 1039 72

Some environmental and genetic factors play important roles in etiopathogenesis of type 1 or insulin-dependent diabetes mellitus (IDDM). HLA genes, the IDDM1 locus located the human chromosome 6, were found to be associated with insulin-dependent diabetes mellitus. However, the incidence of IDDM varied greatly among various populations. To evaluate the pathogenetic factors contributing to the development of IDDM in Taiwan, HLA typing was performed in a group of IDDM unrelated individuals and IDDM pedigrees along with the normal controls from the northern Taiwan. DNA genotypes of class II HLA were done by polymerase-chain-reaction based oligotyping techniques. We confirmed that class II HLA genes were significantly associated with IDDM in Taiwan. To study detailed molecular structure of class II HLA molecules and disease association, we examined several amino acid residues on DQalpha and DQbeta chains and the molecular mechanisms to explain the heterozygotic effect of the DR3/DR4 and DR3/DR9 in the Chinese population. Linkage analysis in our pedigrees confirmed the association between HLA and IDDM in population association studies. Among the several class II alleles, a closer segregation of HLA-DQB1*0401 to the affected persons might suggest that HLA-DQB1*0401 itself or an allele closely linked to the DQB1 locus was the IDDM-predisposing allele in Taiwanese. For IDDM2 (INS) region, association with IDDM was not found due to that more than 90% of the population carried class I alleles. In our collection of IDDM, we found few cases (2.4%) carried mitochondrial DNA mutation. Our studies in Taiwanese confirm a multigenetic nature for IDDM.
Diabetes Res Clin Pract 2000 Oct
PMID:Genetic epidemiology of type 1 diabetes mellitus in Taiwan. 1102 83

We report a case of slowly progressive insulin-dependent diabetes mellitus in an elderly patient with Graves' disease. A 69-year-old man presented with apathetic thyrotoxicosis and weight loss. Laboratory findings indicated insulin-dependent diabetes mellitus (IDDM) with Graves' disease. Human leukocyte antigens DR4 and DR9, which are recognized as markers for IDDM with autoimmune thyroid disease, were detected. The clinical course of the IDDM was compatible with the slowly progressive type. Onset of this disease during old age is rare, and such cases should be analyzed with a thyroid function test because the symptom of thyrotoxicosis may be masked in the elderly.
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PMID:Slowly progressive insulin-dependent diabetes mellitus in an elderly patient with Graves' disease. 1106 48

To further clarify the association of HLA DR alleles with type 1 diabetes mellitus and the influence of age-onset and gender on type 1 diabetes, we investigated HLA-DR in 76 child onset Chinese (36 males) type 1 diabetes patients and 154 normal controls by using PCR-SSP (sequence specific primer). The mean age of onset of diabetes patients was 8.43 +/- 3.96 year-old. Our results revealed that the frequencies of DR3, DR4 and DR9 in diabetes patients were significantly higher than those in control group (all P < 0.01). The susceptible alleles were DR3, DR4, DR9, with relative risks of 8.25, 2.57 and 2.67, respectively. The protective alleles to type 1 diabetes were DR 2, DR8, DR11 and DR12 with relative risk of 0.24, 0.15, 0.16 and 0.39, respectively. There were no significant differences between the frequencies of HLA DR 3, DR4, DR9, DR3/4, DR3/9 and DR4/9 in male and female diabetic children. We divided the diabetes patients into three groups according to their age of onset (1-5 years old, 6-10 years old and 11-17 years old). There was a trend that the frequencies of DR9 decreased with the increase of age at onset, but there was no significant difference of DR3, DR4, DR9, DR3/4, DR3/9 and DR4/9 frequencies between diabetes children with age onset 0-10 years and 11-17 years. As to the influence of gender on the HLA genotypes, the frequency of DR3/4 decreased with the increase of age at onset for male patients and the frequency of DR3/4 increased with the increase of age at onset for female patients.
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PMID:The influence of age and gender on HLA-DR in Chinese child-onset type 1 diabetes mellitus patients. 1122 43

Persistent humoral autoimmunity to the enzyme glutamic acid decarboxylase (GAD) has been described in a substantial proportion of patients with type 1 diabetes mellitus. Higher prevalence of GAD antibody in diabetes patients using a new radioligand-binding assay with recombinant human GAD65 antibodies (GAD65Ab) has been seen in several studies. Using this method, we have reassessed the prevalence of GAD65Ab and investigated the association of GAD65Ab with HbA1C values, C-peptide values, HLA-DR typing and thyroid autoimmune antibody in 70 Chinese children with type 1 diabetes mellitus (mean age of onset 8.21+/-3.84 years, mean duration 3.39+/-2.54 years). Our result revealed that GAD65 antibodies were present in 54.3% (38/70) of diabetes children. There was no significant difference in gender, diabetes onset and duration, HbA1c, C-peptide concentration and frequencies of HLA DR3, DR4, DR9, DR3/DR4, DR3/DR9 and DR4/DR9 genotypes between GAD65Ab+ and GAD65Ab- groups. There was no negative correlation between GAD65Ab values and duration of diabetes in those with GAD65Ab positivity (r=-0.239, P>0.05). The frequencies of antimicrosomal and anti-thyroglobulin antibodies in GAD65Ab+ (13.5,8.1%, respectively) were not different from GAD65- patients (9.4,12.5%, respectively).
Diabetes Res Clin Pract 2001 Oct
PMID:GAD65 antibody prevalence and association with thyroid antibodies, HLA-DR in Chinese children with type 1 diabetes mellitus. 1153 27

The IA-2 is a major autoantigen of type 1 diabetes belonging to the protein tyrosine phosphatase family. We report on the humoral autoimmunity to an alternatively-spliced variant of IA-2 (IA-2 variant) and autoimmune-mediated diabetes age of onset association with IA-2 autoantibody epitope specificities, in 144 recent-onset patients with type 1 diabetes and 54 GAD autoantibody-positive patients with type 2 diabetes. The cytoplasmic domain of IA-2 (IA-2ic) detected a somewhat greater proportion of patients expressing autoantibodies than IA-2 variant (56%vs. 52% of patients with type 1 diabetes and 17%vs. 9% of GAD autoantibody-positive patients with type 2 diabetes). Conversely, only 1% of IA-2 variant autoantibody-positive patients failed to react to IA-2ic construct. Among 80 patients with type 1 diabetes who were positive for autoantibodies to IA-2ic, 8% recognized the juxtamembrane region (JM, representing amino acids 601-629) only, 64% bound the protein tyrosine phosphatase (PTP)-like domain of IA-2 only, and 29% bound both JM and PTP epitopes. Autoantibodies to the PTP-like domain were prevalent in children and adolescents with type 1 diabetes. The age of disease onset in patients with IA-2JM autoantibodies only, was significantly higher than those in patients reacted with the PTP-like domain of IA-2 (P< 0.02). Among GAD autoantibody-positive patients with type 2 diabetes reacted with IA-2ic, 44% bound the JM region only, and 33% bound epitopes in the PTP-like domain only; 22% had autoantibodies to both regions. The frequency of GAD autoantibody-positive patients with type 2 diabetes positive for autoantibodies to the JM region only, was significantly higher than that in patients with type 1 diabetes (P< 0.01). IA-2PTP autoantibodies were significantly associated with HLA-DR4, while the additional reactivity to IA-2JM was associated with HLA-DR9 allele. These results suggest that autoantibody recognition of IA-2 epitopes in autoimmune diabetes is associated with age of disease onset, which may reflect the intensity of the beta-cell destruction process.
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PMID:Association between IA-2 autoantibody epitope specificities and age of onset in Japanese patients with autoimmune diabetes. 1177 57

The diabetes predisposing effect of HLA genes is defined by a complex interaction of various haplotypes. We analyzed the disease association of HLA DRB1-DQA1-DQB1 genotypes in a large nuclear family cohort (n = 622) collected in Finland. Using the affected family based artificial control approach we aimed at characterizing all detectable disease-specific HLA haplotype and genotype effects. The DRB1*0401-DQB1*0302 haplotype was the most prevalent disease susceptibility haplotype in the Finnish population followed by (DR3)-DQA1*05-DQB1*02 and DRB1*0404-DQB1*0302. DRB1*0405-DQB1*0302 conferred the highest disease risk, although this haplotype was very rare. The DRB1*04-DQB1*0304 was also associated with increased disease risk, an effect detected for the first time in the Finnish population. The following haplotypes showed significant protection from the disease and are listed in decreasing order of the strength of their effect: (DR7)-DQA1*0201-DQB1*0303, (DR14)-DQB1*0503, (DR15)-DQB1*0602, DRB1*0403-DQB1*0302, (DR13)-DQB1*0603, (DR11/12/13)-DQA1*05-DQB1*0301, (DR1)-DQB1*0501. In addition to the DRB1*0401/0404-DQB1*0302/(DR3)-DQA1*05-DQB1*02 genotype and DRB1*04-DQB1*0302 homozygous genotypes, heterozygous combinations DRB1*0401-DQB1*0302/(DR13)-DQB1*0604, approximately /(DR8)-DQB1*04, approximately /(DR9)-DQA1*03-DQB1*0303, approximately /(DR1)-DQB1*0501 and approximately /(DR7)-DQA1*0201-DQB1*02 were also disease-associated. As a new finding in this population, the (DR3)-DQA1*05-DQB1*02 homozygous and (DR3)-DQA1*05-DQB1*02/(DR9)-DQA1*03-DQB1*0303 heterozygous genotypes conferred disease susceptibility. Similarly, the DRB1*0401-DQB1*0302/(DR13)-DQB1*0603 genotype was disease predisposing, implying that DQB*0603-mediated protection from diabetes is not always dominant. Comparison of our findings with published data from other populations indicates a significant disease-specific heterogeneity of the (DR8)-DQB1*04, (DR7)-DQA1*0201-DQB1*02 and (DR3)-DQA1*05-DQB1*02 haplotypes.
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PMID:HLA DR-DQ-encoded genetic determinants of childhood-onset type 1 diabetes in Finland: an analysis of 622 nuclear families. 1288 96

The genetic susceptibility for gestational diabetes (GDM) was estimated by comparisons of genotypes within human leukocyte antigen (HLA) and major histocompatibility complex class I chain-related gene A (MICA) in 199 women with GDM and 213 healthy women. At least one of ICA, glutamic acid decarboxylase antibodies, or islet cell antigen-2 antibodies/tyrosine phosphatase antibodies was found in 6.0% (12/199) of women with GDM and were considered as autoimmune GDM, whereas the remaining 187 were considered as nonautoimmune GDM. HLA genotyping was done with polymerase chain reaction and sequence-specific oligonucleotides. MICA polymorphism was determined with polymerase chain reaction and fragment size determination. HLA-DR3-DQ2/x or DR4-DQ8/x and MICA5.0/5.1 were more frequent in autoimmune GDM compared with controls; 92% versus 46% and 42% versus 13% and conferred increased risk (odds ratio [OR] = 13; 95% confidence interval [CI] 1.7-104) and (OR = 4.7; 95%CI 1.4-16). Four other genotypes were more frequent in nonautoimmune GDM compared with controls: HLA-DR7-DQ2/y, 24% versus 14%; DR9-DQ9/y, 9.6% versus 1.9%; DR14-DQ5/y, 7.5% versus 0.94%; and MICA5.0/z, 24% versus 13% and gave increased risk: OR = 2.0; 95%CI 1.2-3.4, OR = 5.6; 95%CI 1.8-17, OR = 8.5; 95%CI 1.9-38, and OR = 2.0; 95%CI 1.2-3.4, respectively. We concluded that autoimmune diabetes with onset during pregnancy is associated with the type 1 diabetes-associated genotypes and also with MICA5.0/5.1, whereas DR7-DQ2/y, DR9-DQ9/y, DR14-DQ5/y, and MICA5.0/z are risk factors for nonautoimmune GDM.
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PMID:Different HLA-DR-DQ and MHC class I chain-related gene A (MICA) genotypes in autoimmune and nonautoimmune gestational diabetes in a Swedish population. 1560 71

To elucidate the genetic factors contributing to heterogeneity of the rate of beta-cell destruction in type 1 diabetes, we investigated the relationship between the time course of complete beta-cell loss and HLA class I and II alleles. HLA allele frequencies were also examined among subgroups classified by the mode of onset. The subjects were 266 type 1 diabetic patients (among whom 196 patients were studied longitudinally) and 136 normal control subjects. Earlier complete loss of beta-cell function was observed in patients who possessed both HLA-A24 and HLA-DQA1*03 and in patients who had HLA-DR9, compared with those without these HLA alleles (P=0.0057 and 0.0093, respectively). Much earlier complete beta-cell loss was observed in the patients who possessed all of HLA-A24, -DQA1*03, and -DR9 compared with the remaining patients (P=0.0011). The combination of HLA-A24, -DQA1*03, and -DR9 showed a higher frequency in acute-onset than slow-onset type 1 diabetes (P=0.0002). In contrast, HLA-DR2 was associated with a slower rate of progression to complete beta-cell loss. These results indicate that the combination of HLA-A24, -DQA1*03, and -DR9 contributes to the acute-onset and early complete beta-cell destruction, whereas HLA-DR2 has a protective effect against complete beta-cell loss in type 1 diabetes.
Diabetes 2006 Jun
PMID:Combination of HLA-A24, -DQA1*03, and -DR9 contributes to acute-onset and early complete beta-cell destruction in type 1 diabetes: longitudinal study of residual beta-cell function. 1673 54


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