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)

The expression of MHC class II determinants (HLA-DR, HLA-DP and Ia7) on peripheral blood monocytes (OKM1+ cells) was studied in 20 children with newly diagnosed IDDM. Monocytes of 10 children with IDDM and familial predisposition showed a statistically significant increase of HLA-DR expression when compared to control group (10 healthy children). There were no significant differences concerning Ia7 expression. HLA-DP expression was similar in all studied groups.
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PMID:MHC class II determinants on peripheral blood monocytes from newly diagnosed IDDM patients. 128 89

We investigated polymorphism of HLA-DP genes in three DR3 related diseases, confirming an association of coeliac disease with a Bgl II DP alpha polymorphism (a restriction fragment sized 3.5 kb present in 75% of patients compared to 34% of control subjects, p less than 0.001), and finding a weaker association with dermatitis herpetiformis (57% v 34%, p = 0.01) and no association with insulin dependent diabetes mellitus. The association with coeliac disease was further investigated. Msp I DP beta polymorphism was studied in 52 healthy subjects and 59 patients: a 4.9 kb fragment was present in 51% of patients with coeliac disease compared to 11.5% of control subjects (p less than 0.001). Furthermore, nearly all subjects with the DP alpha 3.5 kb fragment also had the DP beta 4.9 kb fragment. However, disease frequency was still increased in the DP alpha 3.5 positive/DP beta 4.9 negative group. In seven families, each with at least two affected members, while the DP alpha 3.5 fragment was frequently present in patients it did not preferentially segregate with any particular HLA haplotype--for example, those associated with DR3 or DR7--and therefore is not part of an extended haplotype associated with coeliac disease. We therefore conclude that a gene(s) in the HLA-DP region predisposes to coeliac disease independently of the HLA-DR/DQ regions.
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PMID:HLA-DP and coeliac disease: family and population studies. 197 34

The major histocompatibility complex (MHC) HLA region on chromosome 6p21 contains the major locus of type 1 diabetes (IDDM1). Common allelic variants at the class II HLA-DRB1, -DQA1, and -DQB1 loci account for the major part of IDDM1. Previous studies suggested that other MHC loci are likely to contribute to IDDM1, but determination of their relative contributions and identities is difficult because of strong linkage disequilibrium between MHC loci. One prime candidate is the polymorphic HLA-DPB1 locus, which (with the DPA1 locus) encodes the third class II antigen-presenting molecule. However, the results obtained in previous studies appear to be contradictory. Therefore, we have analyzed 408 white European families (200 from Sardinia and 208 from the U.K.) using a combination of association tests designed to directly compare the effect of DPB1 variation on the relative predisposition of DR-DQ haplotypes, taking into account linkage disequilibrium between DPB1 and the DRB1, DQA1, and DQB1 loci. In these populations, the overall contribution of DPB1 to IDDM1 is small. The main component of the DPB1 contribution to IDDM1 in these populations appears to be the protection associated with DPB1*0402 on DR4-negative haplotypes. We suggest that the HLA-DP molecule itself contributes to IDDM1.
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PMID:The HLA-DPB1--associated component of the IDDM1 and its relationship to the major loci HLA-DQB1, -DQA1, and -DRB1. 1133 27

It is known that certain combinations of alleles within the human leucocyte antigen (HLA) complex are associated with susceptibility or resistance to type 1 diabetes. Variable associations of DR and DQ with type 1 diabetes are documented in Caucasians but rarely in African populations; however, the role of HLA-DP genes in type 1 diabetes remains uncertain. In order to investigate the HLA class II associations with type 1 diabetes in Cameroonians, we used sequence-specific oligonucleotide probing (SSOP) to identify DRB1, DQA1, DQB1 and DPB1 alleles in 10 unrelated C-peptide negative patients with type 1 diabetes and 90 controls from a homogeneous population of rural Cameroon. We found a significantly higher frequency of the alleles DRB1*03 (chi2 = 17.9; P = 0.001), DRB1*1301 (chi2 = 37.4; P < 0.0001), DQA1*0301 (chi2 = 18.5; P = 0.001) and DQB1*0201 (chi2 = 37.4; P < 0.001) in diabetes patients compared to the control group. The most frequent alleles in the control population were DQA1*01, DQB1*0602 and DRB1*15. The DRB1*04 allele was not significantly associated with type I diabetes in our study population. We observed no significant difference between patients and controls in DPB1 allele frequency. In conclusion, the data in Cameroonian diabetes patients suggest the existence of HLA class II predisposing and specific protective markers, but do not support previous reports of a primary association between HLA-DP polymorphism and development of type I diabetes.
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PMID:HLA-DRB1, -DQA1, -DQB1 and DPB1 susceptibility alleles in Cameroonian type 1 diabetes patients and controls. 1153 22

Involvement of gut immune system has been implicated in the pathogenesis of type 1 diabetes. However, few studies have been performed on the gut mucosa from patients with type 1 diabetes. Thus, we characterized the stage of immune activation in jejunal biopsy samples from 31 children with type 1 diabetes by immunohistochemistry, in situ hybridization, and RT-PCR. We found enhanced expressions of HLA-DR, HLA-DP, and intercellular adhesion molecule-1 by immunohistochemistry even on structurally normal intestine of patients with type 1 diabetes and no signs of celiac disease. In addition, the densities of IL-1 alpha- and IL-4-positive cells detected by immunohistochemistry and IL-4 mRNA-expressing cells evaluated by in situ hybridization were increased in the lamina propria in patients with type 1 diabetes and normal mucosa. Instead, the densities of IL-2, gamma-interferon (IFN-gamma), and tumor necrosis factor alpha-positive cells, the density of IFN-gamma mRNA positive cells, and the amounts of IFN-gamma mRNA detected by RT-PCR correlated with the degree of celiac disease in patients with type 1 diabetes. Our study supports the hypothesis that a link exists between the gut immune system and type 1 diabetes.
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PMID:Immunologic activity in the small intestinal mucosa of pediatric patients with type 1 diabetes. 1294 68

To assess the contribution of the HLA class II region for susceptibility to type 1 diabetes mellitus (T1DM), we investigated the association of HLA class II alleles-DP, DQ, and DRB1. Here, we present an extensive molecular typing for HLA class II alleles and their haplotypes in a Bengali-speaking Indian population of T1DM patients (n=151) and controls (n=151) from West Bengal. HLA typing was done by DNA sequencing using a 3730 DNA Analyzer. The individual analysis of each gene gave the following alleles to be higher in cases than in controls, thus making them susceptible alleles-DPA1*020103, DPB1*020102, DQA1*050101, DQA1*0201, and DQB1*020101G. Similarly, the following alleles are protective alleles in our study-DPA1*010602, DPB1*040101, DQA1*010201, DQA1*0103, and DRB1*15. Our result confidently establishes that HLA-DP allelic, and its haplotypic, diversity contributes significantly to the risk for T1DM. The DQA1*0103 allele is a novel allele with a significant association with the protection from T1DM. Among the various haplotypes tested, the DQA1*0201:DQB1*020101G, DQA1*050101:DQB1*020101G, and DQA1*0201:DQB1*030101G were the most frequently found in T1DM patients. In India, very few investigations have been undertaken to study the impact of the genetic background on the risk to develop T1DM in its population, where the annual average incidence is 10.5/100,000/year. In conclusion, the present study highlights the genetic effect of HLA haplotypes that contributes to the susceptibility to T1DM.
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PMID:Role of HLA class II loci polymorphism in the manifestation of type 1 diabetes in a Bengali Indian patient population. 2312 Nov 62

Genes from the HLA complex have a major contribution in type 1 diabetes (T1D), which results from an interplay between environmental and genetic factors. The latter can explain some of the geographic variability in T1D occurrence around the world. Of a particular importance in this regard are the HLA-DR, -DP and -DQ loci. Consequently, we aimed at elucidating the collective genetic profiles of various alleles relating to HLA-DRB1 and -DP in T1D patients throughout the Arab World using the tools of meta-analysis. As for HLA-DQA1 and DQB1 alleles; this analysis was completed and published previously (see Introduction). As a result of limited availability of relevant studies of the HLA-DP locus, only HLA-DRB1 alleles were tackled in this paper. Our study showed that significant increases in T1D risk resulted from harboring the alleles DRB1*03:01 and *04:05 (odds ratio 7.76 and 7.52, respectively). DRB1*04:01 and *04:02 were also predisposing for T1D in Arabs. Very strong evidence supported the protective effects of DRB1*10:01, *13:01, *15:02 and *16:01, with low heterogeneity and no publication bias. The results from the series of meta-analyses performed in this study help to complete the global genetic epidemiological map of T1D by providing statistically robust data from the Arab World.
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PMID:The profile of HLA-DRB1 alleles in Arabs with type 1 diabetes; meta-analyses. 2681 22