A simple nonradioactive method of DNA typing for subsets of HLA-DR4: Prevalence data on HLA-DR4 subsets in three diabetic population groups (original) (raw)
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The Study of Frequencies of HLA-DR3 and DR4 Among Type 1 Diabetes Mellitus Patients
Type 1 diabetes mellitus (T1DM) is so far thought to be an auto-immune disease. This disease has revealed characteristics regarding predisposing factors. One of the genetic predisposing factors is thought to be HLA-DR3 and DR4 genes. The present study aimed at investigating the frequencies of (Human Leukocyte Antigen) HLA-DR3&DR4 genes in a group of 64 Iraqi patients, in whom the T1DM has been already diagnosed and compared to a group of apparently healthy (control group N= 32) individuals. The Real-time PCR was used for the HLA-genes in all members of the study. On the context of genotyping of HLA- allele, DR3 and DR4 were found to be different in their frequencies significantly among T1DM patients that creating high etiological fraction of 0.404 and 0.707 respectively compared to healthy controls, with odd ratio (OR) 4.61 for DR3 and high OR for DR4 26.73. This allele, occurred in high frequencies of the two genes in T1DM patients, was high significantly different between patients group for DR3 compared to healthy group which 51.6% and 18.8% respectively, and very high significantly different between patients group for DR4 compared to healthy group which 73.4% and 9.4% respectively, and both DR3&DR4 also occurred in high significantly difference which 43.8% and 6.3% respectively in T1DM and healthy control group.
HLA-D and -DR antigens in genetic analysis of insulin dependent diabetes mellitus
Diabetologia, 1981
Three groups of patients with insulindependent diabetes mellitus, ascertained by different procedures, were investigated for HLA-A, B, C and D antigens (n = 164), and a subset (n = 93) for HLA-DR. Both HLA-D/DR3 and D/DR4 were strongly positively associated and D/DR2 was negatively associated with insulin-dependent diabetes. HLA-DR4 was found to be a better marker for insulin-dependent diabetes than Dw4. The HLA-B associations (B8, B15 and B18) were clearly secondary to the increases of HLA-D/DR3 and D/DR 4. The HLA associations did not differ between familial and isolated cases indicating that these two groups may well have a common genetic background. Based on analysis of HLA-haplotype sharing in affected sibling pairs, a simple dominant model of inheritance could be ruled out, and a simple recessive model was found unlikely. The relative risks for the HLA-Dw3,4 and HLA-DR3,4 phenotype were 21.2 and 44.4 respectively and exceeded those of both the HLA-Dw3 and HLA-DR3 (5.6 and 4.3) as well as the HLA-Dw4 and DR4 (10.1 and 10.5) phenotypes. This argues against an intermediate genetic model but further studies are needed to clarify whether there is more than one susceptibility gene for insulin-dependent diabetes mellitus within the HLA-system.
A new HLA-DR2 extended haplotype is involved in insulin-dependent diabetes mellitus susceptibility
Human immunology, 1991
To ascertain why HLA-DR2 seems to confer only a moderate re.-.istance to insulin-dependent diabetes mellitus (IDDM) in the high-incidence population of Sardinia, Italy, 32 families having one individual affected with 1DDM (the proband) and 31 families without IDDM history were randomly selected from the same geographical area and serologically and molecularly HLA typed. The 64 haplotypes of the probands were then compared with the 122 haplotypes determined in the parents from the control families. Two haplotypes were found to have the highest percentage in the general population (12.3% and 7.3%, respectively). The first is the already described "Sardinian" extended haplotype A30, CwS, BI8, 3F130, DR3, DRw52, DQw2 (39.0c~ in IDDM patients). The second is an extended haplotype ABBREVIATIONS AA amino acid Asp aspartic acid IDDM insulin-dependent diabetes mellitus
Human Immunology, 1989
Serological HLA typing of 92 insulin-dependent diabetes mellitus (IDDM) patients and 300 healthy controls was performed by the immunomagnetic typing technique. We found an increased risk of IDDM among DR4/w8 heterozygotes, similar to that seen for DR3~4 heterozygotes. The DQ alleles of these DR4/w8 patients were therefore established. When hybridized with a cDNA DQB probe, BamHI-digested DNA from eight out of the nine DR4/w8 patients revealed only one single 10.8-kb DQB
HLA-DR antigens in insulin-dependent diabetes
Archives of Disease in Childhood, 1981
HLA-A, B, C, and DR-typing was performed in 51 children with insulin-dependent diabetes. A close association between childhood diabetes and HLA-DR3 and DR4 was established. DR3 was found in 55% and DR4 in 75% of the diabetic children, compared with 20% and 26% respectively in healthy controls. The combination of DR3 and DR4 was present in 37 % of the diabetic children compared with only 4% of the controls. This investigation provides strong evidence that the susceptibility genes for insulin-dependent diabetes are in close linkage disequilibrium with the HLA-DR locus. In diabetic children DR4 seems to be a more important susceptibility factor than in patients with manifestation of insulin-dependent diabetes after 15 years.
Diabetes Care, 1995
OBJECTIVE To study the human leukocyte antigen (HLA)-DQ heterodimers in the susceptible DR haplotypes for patients with insulin-dependent diabetes mellitus (IDDM) in Taiwan. RESEARCH DESIGN AND METHODS Extended class II HLA haplotypes were studied in 57 unrelated IDDM patients, 31 simplex IDDM families, and 105 unrelated control subjects recruited from the same area in Taiwan. Class II HLA genotyping was based on PCR-SSO DNA typing techniques. Extended class II HLA haplotypes were deduced unequivocally by the Taiwanese pedigree studies. RESULTS DR3/DR3, DR3/DR4, and DR3/DR9 genotypes were strongly associated with IDDM susceptibility in this population. In addition to the reported DR3/DR4 in Caucasians, the heterozygotic effect of DR3/DR9 for IDDM was remarkable in the Taiwanese population. Extended HLA haplotypes studies revealed that DRB1*0301/DQA1*0501/DQB1*0201, DRB1*0405/DQA1*0301/DQB1*0302, and DRB1*0405/DQA1*0301/DQB1*0401 were the susceptible haplotypes in this population. Th...
Tissue Antigens, 1991
We have studied 87 unrelated Caucasian insulin-dependent diabetes mellitus (IDDM) patients and 18 l healthy controls by oligotyping for 20 DRB1, eight DQAl and 13 DQBl alleles, and established their DR-DQ haplotypes and DQ genotypes. An increase of DRBl alleles encoding DR4 was found among IDDM patients, but the distribution of DR4 subtypes did not differ among DR4-positive IDDM patients and controls. The frequency of certain DRB1-DQA1-DQB1 haplotypes and DQA1-DQBl genotypes was significantly increased among IDDM patients. Taken together, the data suggest that IDDM is primarily associated with several (at least five) different DQ ap heterodimers.
Diabetes, 1984
DNA fragments complementary to cloned sequences encoding HLA-D region class II antigen α- and β-chains were determined by genomic blotting with DNA from HLA-typed members of 22 complete families, 12 of which had a proband with insulin-dependent diabetes mellitus (IDDM). Analysis of genotypes showed that the DNA sequences were linked to HLA-DR and permitted confirmation of recombinations in two families. Digestion with the restriction enzymes BamHI, EcoRI, and Pstl and hybridization with an HLA-D region β-chain cDNA probe confirmed a BamHI 3.7 kilobase (kb) fragment present at low frequency among diabetic individuals and a BamHI 3.2 kb fragment that was also decreased among the diabetic subjects compared with siblings (P < 0.05) as well as nonrelated control siblings (P < 0.02) and their parents (P < 0.01). BamHI 12.0 kb (P < 0.05) and 5.8 kb (P < 0.02, P < 0.02), EcoRI 20 kb (P < 0.05, P < 0.02), and Pstl 6.0 kb (P < 0.05) fragments were more frequent in d...
Association of HLA-DQw3 (TA10-) with type I diabetes occurs with DR3/4 but not DR1/4 patients
Diabetes, 1988
We have shown in previous studies that the TA10s ubtype of HLA-DQw3 is significantly increased in HLA-DR4 type I (insulin-dependent) diabetic patients. Data presented in this article indicate that this association only occurs in heterozygous DR3/4 patients and not in DR1/4 patients. Because there is an interactive effect of both DR3/4 and DR1/4 in type I diabetes, the data indicate that the contribution of DR4 haplotypes varies depending on the haplotype borne on the homologous chromosome. In addition, the frequency of the B44-DR4 haplotype was shown to be decreased in DQw3 (TA10) diabetic subjects who were DR3/4 compared with those who were DR1/4 or DR4/x (a pooled group of patients with different DR alleles). This finding suggests that the decrease in the B44-DR4 haplotype in type I diabetes is not solely dependent on its linkage disequilibrium with the DQw3 (TA10+) allele but suggests there is an additional effect exerted independently.