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)

HLA Class II polymorphisms were analysed in 27 families with at least one Type I diabetic proband using Southern blotting technique according to 10th Histocompatibility Workshop Standards. The probes used were DRB, DQA1, DQB1 and DOB. We have studied 108 haplotypes and performed segregation analysis with HLA serology and restriction fragment length polymorphism (RFLP) data and compared "affected" with "non-affected" haplotypes (not inherited by IDDM patients). RFLPs correlated well with DR and DQ serology and detected additional polymorphisms. In particular, DQB polymorphism analysis showed segregation of the DQw3 splits with 88.5% of the DR4 affected haplotypes bearing the DQw3.2 split (now DQw8) and 11.5% the DQw3.1 split (now DQw7) while in the non-affected DR4 haplotypes 33.3% were DQw3.2 and 66.6% were DQw3.1. Haplotype analysis showed that DR4-DQw3.2 was in strong linkage with the U fragment (2.1 kb Taq I) of DQA2 (DX alpha) and with the L fragment (5.4 kb BamH I) of DOB. This study confirms previous observations of DQB polymorphisms in heterozygous IDDM patients, supports the protective effect of DQw3.1 (DQw7) against the development of the disease and demonstrates the importance of DQw3.2 (DQw8) for susceptibility to Type I diabetes.
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PMID:Restriction fragment length polymorphism analysis of HLA haplotypes in families with type I diabetes mellitus. 196 92

Genetic variation of the DQ alpha and beta and of the DX alpha genes, detectable as RFLP in genomic DNA digests, has been suggested to improve the identification of individuals at high risk for insulin-dependent diabetes mellitus (IDDM). DNA from all members of 32 IDDM multiplex families was digested with six restriction endonucleases and the resulting fragments analyzed in Southern blots for hybridization with labeled cDNA probes for those genes. A computerized segregation analysis procedure was then used to assign fragments to haplotypes. Associations among fragments and between fragments and haplotypes characterized serologically and biochemically for their class II genes and IDDM-carrier status were calculated. The results indicate that the alleles of the DX alpha polymorphism maintain linkage disequilibrium with those of the DQ beta genes responsible for the well-known DQ beta 3.2-IDDM association, so that IDDM-carrier haplotypes carry disproportionally often both DQ beta 3.2 and DX alpha-TaqI-2.2kb. Thus, these RFLPs identify a DR-DQ-DX haplotype in high linkage disequilibrium, rather than the locus or loci that account for their high relative risk. However, four DR4-DQ beta 3.2 haplotypes that lack DX alpha-TaqI-2.2kb were encountered, two of which are "affected." These haplotypes suggest that the identification of the "disease locus" can be facilitated by the study of unusual haplotypes in which distinct IDDM-associated alleles occur separated from their neighbors of the standard genetic configurations.
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PMID:Definition of IDDM-associated HLA DQ and DX RFLPs by segregation analysis of multiplex sibships. 256 60

Fibrocalculous pancreatic diabetes (previously known as tropical pancreatic diabetes) is a rare cause of diabetes confined to countries within the tropical belt. The aetiology of fibrocalculous pancreatic diabetes is thought to be environmental although the agent(s) is unknown. We have investigated a possible genetic basis of this disease by looking for restriction fragment length polymorphisms of genes implicated in the aetiology of diabetes mellitus. Seventy-six Dravidian patients with fibrocalculous pancreatic diabetes were studied, and the restriction fragment length polymorphisms obtained compared to racially matched control subjects (n = 94), patients with Type 2 (non-insulin-dependent) diabetes (n = 87) and Type 1 (insulin-dependent) diabetes (n = 58). No association of fibrocalculous pancreatic diabetes was found with restriction fragment length polymorphisms of the insulin receptor gene. Although no association of fibrocalculous pancreatic diabetes was found with polymorphism of the HLA DR alpha/DQ alpha/DX alpha genes, an association was found with the Taq 1 restriction fragment length polymorphisms of the DQ beta gene (DQ beta T2/T6 present in 39% of patients with fibrocalculous pancreatic diabetes compared to 19% in control subjects; p = 0.01; corrected p value = 0.04) which is similar to that found in Type 1 but not Type 2 diabetes. An association of fibrocalculous pancreatic diabetes was also found with the hypervariable region in the 5-prime flanking region of the insulin gene; 40% of patients possessed the class 3 allele compared to 9.5% of control subjects p = 0.0001; corrected p value = 0.0008).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The genetic predisposition to fibrocalculous pancreatic diabetes. 824 80

HLA-DQ alpha and HLA-DX alpha gene polymorphisms were analyzed by Southern blot techniques in 78 Caucasoid insulin-dependent diabetes mellitus (IDDM) subjects and 55 control subjects. Five restriction fragment length polymorphisms of the HLA-DQ alpha gene correlated with HLA-DR typing. Two allelic DX alpha-related gene fragments, of 2.1 kb (U) and 1.9 kb (L) in size were identified. Genotype frequencies in the IDDM group for UU, UL, and LL were 54%, 38.5%, and 7.5%, respectively, whereas the corresponding frequencies in the control group were 24%, 40%, and 36% (P less than 0.00005 for differences in genotype frequencies). The U allele was associated particularly with IDDM patients who were DR3, with healthy controls who were DR3, as well as with IDDM patients who were not DR3. Thus, if this DX alpha U allele is not the DR3-associated IDDM susceptibility gene, it is the closest marker hitherto studied.
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PMID:A DR3-related DX alpha gene polymorphism strongly associates with insulin-dependent diabetes mellitus. 300 76

Genetic studies indicate that the IDDM susceptibility genes in the HLA region are closely linked to the DR3 and DR4 specificities; however, these specificities do not define the actual susceptibility genes. Molecular studies confirm this hypothesis by demonstrating restriction fragment length polymorphism between DNA's of identical DR specificities and thereby separating the DR haplotypes into those strongly or weakly associated with IDDM. Further studies at the nucleotide sequence level demonstrate further heterogeneity, with DR4 being associated with at least three different DQ beta genes and five different genes of the DR beta-1 locus. However, the majority of these subtypes are now recognized either serologically or by T-cell responses in mixed lymphocyte cultures. Furthermore, the sequences associated with IDDM are those most commonly found in DR4 individuals, ie, Dw4 and DQw3.2. Clearly, these and other class II genes must be studied for additional DNA polymorphism and their relevance for IDDM. For example, the DX alpha, 2.1-kb Taql polymorphism shows a stronger correlation with IDDM than DR3. However, it is not even known if the DX alpha genes are expressed. In addition, little is known of the DQ beta and DR beta genes associated with different DR3-associated haplotypes. Furthermore, an IDDM susceptibility gene may contain important differences in flanking or intron sequences controlling expression of these genes. The methods of recombinant DNA technology are enabling these unanswered questions to be addressed.
Diabetes Metab Rev 1987 Jul
PMID:Molecular biology of the HLA system in insulin-dependent diabetes mellitus. 330 Dec 40

Genetic associations with Type 1 (insulin-dependent) diabetes may be primary or secondary to linkage disequilibrium. Studies of different racial groups should allow these to be distinguished. We have reported that Type 1 diabetes is associated with HLA-DR3 and -DR4 in subjects of North Indian (Punjab) origin and now present the results of a study of HLA class II DNA polymorphisms in this group and in white caucasoid subjects. DR4 in North Indian Type 1 diabetic patients was associated with DQ beta and DX alpha DNA polymorphisms identical to those found in DR4-positive white caucasoid patients. This DQ beta/DX alpha pattern was increased in frequency in North Indian diabetic patients vs control subjects (33.3% vs 8.5%, p less than 0.001, relative risk = 5.12 (95% confidence limits: 1.96-13.4)). A DQ beta polymorphism with very low relative risk for Type 1 diabetes in white caucasoid subjects was also markedly reduced in North Indian diabetic patients vs control subjects (2.3% vs 24.7%, p less than 0.02, relative risk = 0.10 (95% confidence limits: 0.02-0.46)). This pattern was associated with DR2 in white caucasoid subjects, but with DRw6 in North Indians. A DR3-associated DR beta polymorphism was markedly increased in North Indian diabetic patients vs control subjects (90.2% vs 40.7%, p less than 10(-6), relative risk = 12.1 (95% confidence limits: 4.32-33.9)). The DQ subregion may be a primary site of genetic influence on susceptibility to Type 1 diabetes. Further studies in different racial groups will clarify the HLA associations of Type 1 diabetes.
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PMID:Class II HLA DNA polymorphisms in type 1 (insulin-dependent) diabetic patients of north Indian origin. 341 56