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)

Aldose reductase (ALR2), the first enzyme of the polyol pathway, may plan an important role in the pathogenesis of diabetic microvascular complications. The gene coding for ALR2 has been localized to chromosome 7q35. Using an ALR2 probe in conjunction with the restriction endonuclease Bam-HI, we have investigated the ALR2 locus of 128 patients with type I diabetes. A significant decrease in the frequency of the 8.2 kilobase (kb) Bam-HI ALR2 genotype and 8.2 kb allele was found in patients with nephropathy (nephropaths) compared to those with retinopathy alone (retinopaths) (p < 0.05 and 0.25, respectively). We have previously shown that an RFLP of the T-cell antigen receptor constant beta-chain (TCRBC) locus, which is also localized to chromosome 7q35, is strongly associated with susceptibility to microvascular complications. The 128 patients were genotyped using the restriction endonuclease Bgl-II and a TCRBC probe. The 10/9.2-8.2 kb TCRBC-ALR2 genotype was significantly decreased in the nephropaths compared to the retinopaths (13.7% versus 43.6%, chi 2 = 10.1, p < 0.0025). The 10/9.2 and 9.2/9.2 kb TCRBC-ALR2 haplotypes were increased in the nephropaths compared to the retinopaths (32.5% versus 8.9% chi 2 = 10.9, p < 0.001). These results suggest that chromosome 7q35 harbors a gene(s) that is involved in the pathogenesis of microvascular complications. Interestingly, the gene coding for endothelial nitric oxide synthase has recently been localized to the same chromosomal region as ALR2.
J Diabetes Complications
PMID:Chromosome 7q35 and susceptibility to diabetic microvascular complications. 877 31

To examine the association between von Willebrand Factor (vWF) concentrations and features of the insulin resistance syndrome, 208 patients with Type 2 (non-insulin-dependent) diabetes (NIDDM) and 80 healthy controls were studied. A restriction fragment length polymorphism in exon 12 of the vWF gene, detected by Aat II endonuclease, was also examined. vWF concentrations were elevated in the patient group (patients 1.28 IU ml-1 vs controls 1.12 IU ml-1, p = 0.003). Genotype frequencies were in Hardy-Weinberg equilibrium and genotype did not relate to vWF levels: means (95% CI) were AA 1.29 (1.29-1.44) IU ml-1 n = 3; AG 1.28 (1.22-1.26) IU ml-1 n = 48; GG 1.29 (1.25-1.39) IU ml-1 n = 155. vWF correlated with age (r = 0.23 p < 0.0005), duration of diabetes (r = 0.23, p < 0.001), and fibrinogen (r = 0.22, p = 0.002) in the patient group, but was unrelated to blood lipids, HbA1C, body mass index, glucose, hypertension, and smoking. In a linear regression model, age and insulin remained as independent predictors of vWF levels, explaining 16% of inter-individual variance in the patient group. In conclusion, these findings show vWF concentrations are elevated in NIDDM and are weakly related to features of the insulin resistance syndrome. No relationship was demonstrated between the gene polymorphism studied and vWF concentrations in this group.
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PMID:Levels of von Willebrand factor, insulin resistance syndrome, and a common vWF gene polymorphism in non-insulin-dependent (type 2) diabetes mellitus. 886 46

The ability of beta cells to endure assaults by various environmental agents, including toxins and viruses, may be relevant to the development of diabetes. We have examined the mode of cell death caused by streptozotocin (STZ) in a murine pancreatic beta cell line, INS-1. Apoptosis was identified by detection of initial endonuclease-mediated DNA strand breaks by DNA gel electrophoresis. Apoptosis and necrosis were distinguished morphologically by light and electron microscopy. Higher rates of apoptosis, as compared to necrosis, were observed when cells were exposed to 15 mM STZ for 1 hr followed by a 24 hrs recovery period. Higher doses of STZ (30 mM) caused the cells to undergo necrosis (22%) as well as apoptosis (17%). These results suggest that the cytotoxic effect of STZ, at low doses, on beta cells involves the activation of the apoptotic pathway, whereas, at high doses, the mode of beta cell death is predominantly necrosis.
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PMID:Streptozotocin at low doses induces apoptosis and at high doses causes necrosis in a murine pancreatic beta cell line, INS-1. 887 77

We have studied the genotypic, haplotypic, and allelic distribution of germline Restriction Fragment Length Polymorphism (RFLP) of T-cell receptor (Tcr) alpha, gamma, and delta loci in 75 insulin-dependent diabetes mellitus (IDDM) patients and 84 healthy blood donors as control population. The restriction endonuclease PvuII produces three allelic fragments of Tcr C gamma (TcrCG) gene segment of 16, 13, and 11.3 Kb respectively. Our observations revealed that PvuII/TcrCG RFLP allelic distributions were not significantly different in the IDDM and the control group. However, 85% of IDDM patients carried HLA DR3 and/or DR4 haplotypes, and when comparing these patients with a second group of HLA DR3+ and/or DR4+ healthy individuals, the 11.3 Kb/PvuII fragment of TcrCG gene was found to be associated with IDDM patients (chi 2 = 11.4, P = 0.003). 54.9% of IDDM patients carried at least one 11.3 Kb allele vs. 21% in controls (chi 2 = 10.77, P = 0.004). No significant association was found between RFLP in Tcr, C alpha, C delta, V gamma 9 loci and IDDM.
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PMID:T-cell receptor alpha, delta, and gamma chain genes in insulin-dependent diabetes mellitus. 909

Since recent studies demonstrated the occurrence of the mitochondrial DNA (mtDNA) mutation A3243G in patients with adult-onset diabetes, an investigation was undertaken to determine the frequency of this mutation in a pediatric population with insulin-dependent diabetes mellitus (IDDM). DNA was extracted from peripheral blood of 270 pediatric patients with IDDM. The presence of the mtDNA A3243G mutation was screened for by minisequencing and mutation-specific ApaI endonuclease restriction after polymerase chain reaction (PCR) amplification of mtDNA. The A3243G mtDNA mutation was not found in any IDDM patients examined. This mutation is uncommon in children with IDDM from various ethnic and racial groups. Therefore, the contribution of the mutation to the pathogenesis of IDDM, if any, is minimal.
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PMID:Screening for the mitochondrial DNA A3243G mutation in children with insulin-dependent diabetes mellitus. 910 52

To identify diabetes mellitus caused by the mitochondrial gene substitution at genomic nucleotide pair 3243 (M3243A-->G) we selected 87 diabetic patients with high risk factors such as maternal inheritance and hearing loss. Total DNA was extracted from peripheral leukocytes, and mitochondrial DNA fragments containing M3243A-->G were amplified by polymerase chain reaction (PCR). The amplified fragments were digested with a restriction endonuclease Apa1 and analyzed by agarose gel electrophoresis. The incidence of the M3243A-->G mutation was 4.6% (four of 87) in diabetic patients with maternal inheritance and/or hearing loss. In a subgroup with both maternal inheritance and hearing loss, the incidence of the mutation was as high as 21.4% (three of 14). Cardiac disorders were also present in all four diabetic patients with the mutation. This study suggests that maternal inheritance and hearing loss are useful clinical findings to identify diabetic patients with the mutation, and that cardiac involvement is a high risk factor for the M3243A-->G mutation.
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PMID:High prevalence of mitochondrial diabetes mellitus in Japanese patients with major risk factors. 922 33

Familial hypobetalipoproteinemia is an autosomal co-dominant disorder, which in a minority of cases is due to a truncation producing mutation in the apoB gene. We have identified an apoB mutation in a 40-year old hypobetalipoproteinemic man with Type II diabetes mellitus. Immunoblotting of plasma revealed a major band for apoB-100 and a minor band with estimated size between apoB-52 and apoB-55. The proband's 75-year old father with Type II diabetes and a non-diabetic daughter also possessed the truncated protein. Direct sequencing of the amplified fragment of genomic DNA revealed a C-->T transition at nt 7692 in exon 26 of the apoB gene. This substitution yielded a premature stop codon at residue 2495 and abolished a BsaI restriction endonuclease site. The identical mutation has been described previously; however, the genotypes and ancestors of the kindred were different, suggesting that the mutation may have occurred independently. The majority of apoB-55 was eluted as particles smaller than LDL-sized apoB-100, and floated mostly between the LDL and HDL density range. It is worth noting that despite the presence of Type II diabetes, both the proband and his father have very low plasma lipid levels and neither have any clinically manifest macrovascular complications.
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PMID:Diabetes mellitus in a new kindred with familial hypobetalipoproteinemia and an apolipoprotein B truncation (apoB-55). 954

Adynamic bone disease unrelated to aluminum deposition, with low parathyroid hormone (PTH) levels, has increased in patients with end-stage renal failure. Some patients present with severe secondary hyperparathyroidism despite calcitriol administration and phosphate restriction. Because therapeutic and environmental factors are now similar among hemodialyzed patients, the variable incidence of secondary hyperparathyroidism may be caused by genetic heterogeneity. To examine this possibility, we analyzed restriction fragment length polymorphisms of the vitamin D receptor (VDR) gene in 877 Japanese hemodialysis patients. VDR allelic polymorphism was determined by the method of Morrison et al. Polymerase chain reaction (PCR) amplification and a BsmI endonuclease restriction site at the 5' end of the VDR gene defined BB (absence of restriction site on both alleles), Bb (heterozygous), or bb (restriction site on both alleles). The mean serum PTH level was lower in BB patients (86 +/- 102 pg/mL) than in bb patients (148 +/- 217 pg/mL; P < 0.05). The serum osteocalcin level was also lower in BB than in bb patients (P < 0.05). If results were re-analyzed excluding patients with a history of dialysis exceeding 10 years or those with non-insulin-dependent diabetes mellitus (NIDDM) or who had undergone parathyroidectomy, the differences in serum PTH levels were greater. However, there was no significant difference in serum PTH levels among the VDR genotypes, only for patients with NIDDM. The present study shows that patients with the b allele for the VDR gene have more severe secondary hyperparathyroidism than patients without the b allele. However, NIDDM or a long history of hemodialysis has a stronger power to influence PTH secretion.
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PMID:Vitamin D receptor gene polymorphisms affect secondary hyperparathyroidism in hemodialyzed patients. 974 Jan 63

In two German families four patients containing the A3243G mutant in the mitochondrial DNA suffered from maternally-inherited diabetes and deafness (MIDD). DNA was isolated from oral mucosa cells. Using the polymerase chain reaction with not yet published primers, we obtained after digestion with the restriction endonuclease BSP 1201 two oligonucleotides of comparable size increasing the sensitivity of our method two times. Under these conditions we were able to detect 0.8% of the mutated DNA. In general, the patients show the characteristics proposed for MIDD by Maassen et al. (1997), however, there are some differences: age at onset (in our study 36-45 y), body mass index (>26 kg/m2). In addition, our study shows that MIDD may be combined with neuronal disorders (M. Parkinson, epilepsy) and/or endocrinopathies (M. Addison). Our data indicate that MIDD is a heterogeneous disease. On the other hand, in one family there are healthy probands with a high concentration of mutated mitochondrial DNA.
Exp Clin Endocrinol Diabetes 1998
PMID:Maternally-inherited diabetes and deafness: report of two affected German families with the A3243G mitochondrial DNA mutation. 983 3

We found a novel A-->G change at nucleotide 1968 within the 3'-untranslated region of the HNF1B gene encoding the hepatocyte nuclear factor-1 beta. The HNF1B 1968A/G polymorphism could be detected by digestion with endonuclease MspI. The frequency of the HNF1B 1968G allele was 0.060 in Caucasians and 0.129 in Canadian Oji-Cree. Because of the importance of the HNF1B gene product in the regulation of transcription of several hepatic proteins, this polymorphism may be useful in the study of associations with metabolic phenotypes such as diabetes.
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PMID:Human hepatocyte nuclear factor-1 beta (HNF1B) 1968A/G polymorphism. 1072 73


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