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)

Islet-cell antibodies have been reported to be of predictive value for the future development of Type 1 (insulin-dependent) diabetes in first degree relatives of diabetic patients with the risk increasing in these subjects with the islet-cell antibodies titre. However, very little is known about islet-cell antibodies in background populations. Sera (n = 8363) from schoolchildren (6-17 years) in the French background population were screened for the presence of islet-cell antibodies by the indirect immunofluorescence technique. Islet-cell antibodies greater than 4.5 Juvenile Diabetes Foundation units were found in 150 sera (prevalence rate 1.8%; 95% confidence interval 1.5-2.1%). Only 17 sera demonstrated islet-cell antibody titre greater than or equal to 24 JDF units. No particular feature was found to be significantly different between islet-cell antibody-positive and islet-cell antibody-negative children (age, family history of diabetes, fasting plasma glucose, insulin autoantibodies). A second blood sample was obtained from 80 of 150 islet-cell antibody positive children after a mean interval of 8 months. Only 11 sera became less than 4.5 JDF units with islet-cell antibody titres being stable in the remaining sera, including the high-titre positive sera (greater than or equal to 24 JDF units). HLA-DQB typing was performed by restriction mapping techniques in 80 islet-cell antibody-positive, in 93 islet-cell antibody-negative and in 213 Type 1 diabetic children. The distribution of the susceptibility alleles (DQB1-Asp57-negative) was not significantly different between islet-cell antibody-positive and islet-cell antibody-negative children.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Islet cell antibodies in normal French schoolchildren. 161 32

The allelic forms of the HLA-DQB gene have been recognized as susceptibility markers of type 1 diabetes mellitus. One of these alleles, the DQw3.2 (DQw8), accounts for the well-documented association of the DQw3 locus with the disease. This report describes a method using the polymerase chain reaction mismatch technique to amplify the three different DQw3 allele sequences in 26 insulin-dependent diabetic patients. Primers were designed that differed only at one base at the growing end of their sequences. Using a common oligonucleotide primer located downstream in the first domain of the DQB gene and three other primers located at the other end of the sequence being amplified, it was possible to identify and distinguish the DQw8 allele from the other two closely related alleles (DQw7, DQw9). This method, which could be useful in excluding HLA-related susceptibility to diabetes mellitus, is rapid and nonisotopic, and indeed could be adapted to investigate any DNA sequence polymorphism.
 ...
PMID:Use of the polymerase chain reaction mismatch technique to identify the HLA-DQw8 allele in patients with insulin-dependent diabetes mellitus. 172 61

HLA class II associations with IDDM in populations of non-Caucasoid origin can provide important insights into the nature of the HLA and disease association. Firstly, HLA class II alleles that are rare in Caucasoids but common in other populations can be assessed for their contributory role in IDDM. Secondly, the different HLA class II gene linkage arrangements in different populations can help map the IDDM susceptibility determinants. This chapter reviews studies of HLA class II associations with IDDM in Asian Indians, Chinese, Japanese, Africans and black Americans. Most of these studies have been based on HLA-DR serology. However, DNA analyses, based on restriction fragment length polymorphism, sequence specific oligonucleotide hybridizations of polymerase chain reaction products and DNA sequencing, have made clear the identity of genes contributing to susceptibility or resistance to IDDM in populations of non-Caucasoid origin. DNA sequence analysis of the variable regions of the HLA-DQA, DQB and DRB genes has revealed at least eight alleles at HLA-DQA, 13 at HLA-DQB and 34 at HLA-DRB1. This chapter correlates HLA-DR and DQ allelic diversity with inherited predisposition to IDDM on a global basis. IDDM is strongly associated with the serological specificities of HLA-DQ, rather than with particular amino acid substitutions in class II alleles. DQw8 has a high risk for IDDM, DQw4, DQw5 and DQw9 have a lesser risk, while DQw6 and DQw7 are protective in IDDM. DQw2 is permissive for IDDM, depending on the presence of other HLA class II alleles. Increased heterozygosity at HLA is observed in Oriental patients, as it is in Caucasoid IDDM patients. The nature of this synergism is examined in terms of possible interactive effects between DQA and DQB alleles or DRB and DQB alleles; both effects could be operating. The conclusion from this genetic analysis is that molecular mimicry at HLA-DQ, with either foreign or autoantigens, may be an important mechanism in IDDM. Additionally, the anomalous role of DQw2 in IDDM suggests that a further mechanism, such as T cell activation, may control the ability to mount an immune response against autoantigens. Further studies, possibly with transfectant cell lines, are necessary to clarify the functional role of HLA class II genes in IDDM.
 ...
PMID:Cross-ethnic group comparisons of HLA class II alleles and insulin dependent diabetes mellitus. 189 68

Food antigens and enteroviruses are possible triggers of type 1 diabetes. Because permeability of the intestinal epithelium may facilitate contact of these antigens with the mucosal immune system, we set out to study intestinal permeability in patients with type 1 diabetes. Children with type 1 diabetes (n = 26, mean age 12 years, mean duration of disease 4 years) and 24 healthy age-matched control children were given mannitol and lactulose orally, and their intestinal permeability was measured as a percentage of this dose recovered in urine. Patients with type 1 diabetes did not differ in their permeability to lactulose, nor was their lactulose/mannitol ratio any different from that of controls. However, patients with type 1 diabetes who had the HLA-DQB 1*02 allele and, therefore, a higher risk for celiac disease (CD) absorbed significantly more mannitol (mean + 95% CI): 17.7% (15.2-20.2) than did those negative for this allele: 12.3% (8.2-16.4), p = 0.04. Their lactulose permeability was also higher: 0.30 (0.16-0.44) and 0.09% (0-0.18), respectively, p = 0.02. Although the differences in permeability reach statistical significance, there was still much overlap between the two groups in terms of actual laboratory values. The higher permeability of patients with the HLA-DQB1*02 allele suggests that these patients may be more prone to develop abnormal immune responses to food antigens.
 ...
PMID:Intestinal permeability to mannitol and lactulose in children with type 1 diabetes with the HLA-DQB1*02 allele. 1251 91