Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin promoter factor 1 (IPF-1) is a homeodomain-containing protein that is thought to be a key regulator of pancreatic islet development and insulin gene transcription in beta-cells. This report describes the isolation and characterization of the human IPF-1 gene. The coding region, which showed 83% nucleotide identity with the mouse IPF-1 gene, was encoded by two exons that extended over a 5-kb region of human genome. The deduced human IPF-1 protein contained 283 amino acids, 1 amino acid less than the mouse IPF-1 protein. The homeodomain region of IPF-1 was encoded by the second exon, and it was highly conserved among species. The human IPF-1 gene was mapped to chromosome 13q12(12.1) by fluorescent in situ hybridization (FISH) analysis. A simple sequence repeat polymorphism (ipf1CA2) was identified in the genomic clone. Polymerase chain reaction (PCR) amplification of this repeat region revealed two alleles (heterozygosity = 0.32). This simple sequence repeat polymorphism, and thus the IPF-1 gene, was incorporated into the human linkage map by genotyping reference Human Polymorphism Study Center (CEPH) pedigrees. Multipoint analysis with the CEPH genotype database placed the gene with equal likelihood between two marker intervals: D13S292-cdx3GA1 and cdx3GA1-D13S289 on chromosome 13, consistent with the results of FISH analysis. Two-point linkage analysis inferred that the most likely location for ipf1CA2 was at theta = 0 from cdx3GA1 locus. The exon-intron boundaries of the IPF-1 gene were sequenced, and primers were synthesized to search the homeodomain region for potential variants in patients with NIDDM. By single-strand conformational polymorphism analysis, no variants were found within this region in 61 Japanese patients, which could contribute to the pathogenesis of NIDDM. The isolation of the human IPF-1 gene, along with characterization of its genomic structure and chromosomal mapping, will now permit the assessment of the role of this gene in the pathogenesis of NIDDM in various populations.
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PMID:Isolation, characterization, and chromosomal mapping of the human insulin promoter factor 1 (IPF-1) gene. 863 54

We investigated the relationship between advanced diabetic retinopathy (ADR) and an angiotensin-converting enzyme (ACE) gene polymorphism in subjects with type 2 diabetes and ADR, pre-proliferative (PrePDR) or proliferative diabetic retinopathy (PDR) without overt nephropathy. Polymerase chain reactions were used to detect insertion/deletion (I/D) polymorphisms of the ACE gene. There was no difference in the frequency of II, ID, or DD genotypes, or of I and D alleles among subjects with type 2 diabetes without diabetic retinopathy (NDR) or with simple diabetic retinopathy (SDR) and non-diabetic controls. There was also no difference in the frequency of ACE genotypes among subjects with type 2 diabetes with NDR, or SDR and ADR. However, the frequency of the ACE DD genotype in ADR was significantly higher than that in controls (chi(2)=6.64, P=0.036). On the other hand, the frequency of the D allele in ADR was significantly higher than that in controls (chi(2)=6.33, P=0.012), NDR (chi(2)=4.18, P=0.041) and SDR (chi(2)=4. 89, P=0.027), respectively. These results indicate a significant relationship between the presence of the D allele polymorphism in the ACE gene and ADR in Japanese subjects with type 2 diabetes and no overt nephropathy.
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PMID:Detection of the association between a deletion polymorphism in the gene encoding angiotensin I-converting enzyme and advanced diabetic retinopathy. 1110 34

To investigate the genetic susceptibility associated with cough related to angiotensin-converting enzyme inhibitor (ACEI) therapy in patients with type 2 diabetes, 189 non-insulin-dependent diabetes mellitus (NIDDM) patients with proteinuria or hypertension treated with perindopril were studied. Cough was considered to be present if the patients had been bothered by a cough during treatment and if they had had related symptoms for at least 2 weeks without an identifiable cause. Polymerase chain reaction (PCR) coupled with single-strand conformation polymorphism (SSCP) was used to detect polymorphisms of ACE and bradykinin B2-receptor genes. After 8 weeks of treatment, 49.2% (93 of 189) of our NIDDM patients were found to be suffering from ACEI-related cough. ACEI-related cough was mainly associated with female patients, with 71.7% (76 of 106) of female and only 20.5% (17 of 83) of male patients experiencing cough after ACEI treatment. There was a significant association of ACE II genotype with ACEI-related cough. The genotype frequencies were 58.2% for II, 47.8% for ID, and 16.7% for DD in patients with ACEI-associated cough and 41.8% for II, 52.2% for ID, and 83.3% for DD in subjects without ACEI-associated cough (chi(2) = 10.268; df = 2, P =.006). As female patients made up the majority of the subjects suffering from ACEI-related cough, we further analyzed the association of ACE I/D genotype with ACEI-related cough separately by sex. Male patients with ACEI-related cough were not associated with ACE I/D genotype distribution, while female patients were strongly associated with ACE I/D genotype polymorphism (chi(2) = 16.12; df = 2; P <.001). There was no association between the bradykinin B2 receptor gene -58T/C polymorphism with ACEI-related cough. In conclusion, our results indicate that Chinese diabetic female subjects are susceptible to ACEI-related cough, and this susceptibility may be genetically predetermined.
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PMID:Angiotensin-converting enzyme gene insertion/deletion, not bradykinin B2 receptor -58T/C gene polymorphism, associated with angiotensin-converting enzyme inhibitor-related cough in Chinese female patients with non-insulin-dependent diabetes mellitus. 1169 55

A total of 361 Chinese patients with type 2 diabetes were studied for the association between peripheral vascular disease (PVD) and the insertion/deletion polymorphism involving a 287-bp alu repeat sequence at intron 16 of the angiotensin-converting enzyme (ACE) gene. The patients were divided into PVD (+) (n=45) and PVD (-) (n=316) based on an ankle-brachial index <0.9 and > or =0.9, respectively. Polymerase chain reaction was used to identify gene polymorphism. Results showed that D allele frequency in the patients without and with PVD was 31.8% and 33.3%, respectively (p=NS). The prevalence rates of II, ID and DD genotypes in the PVD (-) group were 45.6%, 45.3% and 9.2%, respectively; and the respective values for the PVD (+) group were 44.4%, 44.4% and 11.1% (p=NS). Prevalence rates of PVD in genotypes II, ID, and DD were 12.2%, 12.3% and 14.7%, respectively (p=NS). In logistic regression analyses, the unadjusted and adjusted odds ratios for DD vs II and ID vs II genotypes for PVD were not statistically significant. The respective adjusted odds ratios were 1.88 (0.56-6.29) and 1.33 (0.63-2.80). In conclusion, there was not a significant association between the ACE genotype and PVD in Chinese type 2 diabetic patients. However, a type 2 error can not be ruled out.
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PMID:Lack of association between angiotensin-converting enzyme gene polymorphism and peripheral vascular disease in type 2 diabetic patients in Taiwan. 1241 32

The most common alterations in lipid and lipoprotein metabolism in type 2 diabetes involve an elevation in both plasma triglyceride and VLDL concentrations, a dense LDL phenotype and low levels of HDL cholesterol. The inverse relationship between the level of HDL cholesterol and the risk of cardiovascular disease is commonly explained by the crucial role of HDL in reverse cholesterol transport. Cholesterol ester transfer protein (CETP) has a central role in the metabolism of HDL and may therefore alter the susceptibility to atherosclerotic vascular disease. To evaluate the effect of Taq1B polymorphism of intron 1 of CETP gene on serum lipid concentrations in Turkish type 2 diabetic patients, we investigated Taq1B polymorphism and serum lipid levels in 116 controls and in 164 diabetic patients. Polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine the CETP Taq1B polymorphism. Serum lipid levels were measured enzymatically. Statistical analyses was performed by SPSS. In control group: subjects with B2B2 genotype have high HDL-cholesterol levels (p=0.029) and B1B1 genotypes have high triglyceride levels (p=0.07). Diabetic patients with and without MI with B2B2 genotype have high HDL-cholesterol levels. Taq B1B1 genotype has higher in diabetic patients with myocardial infarction (MI) than diabetic patients without myocardial infarction (42.1% and 32.7%; chi2=1.42, p=0.23). The present study demonstrates that the CETP Taq1B gene polymorphism is an association with low HDL cholesterol levels in patients with type II diabetes mellitus and healthy controls in Turkey. We also showed that CATE Taq1B gene polymorphism may be related to myocardial infarction in type II diabetic patients.
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PMID:Taq1B polymorphism of CETP gene on lipid abnormalities in patients with type II diabetes mellitus. 1513 31

To study whether the 3c/t polymorphism of the sulfonylurea receptor 1 (SUR1) gene exon16 increased the risk of type 2 diabetes mellitus in type 2 diabetes mellitus pedigrees in Han population in south area of China. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used in 46 type 2 diabetes mellitus pedigrees. The polymorphism in SUR1 was tested and analyzed by Mantel-Haenszel chi(2) test. Frequencies of SUR1-3c/t polymorphism had no significant difference between type 2 diabetes mellitus and normal relatives (genotypes chi(2)=3.224, P=0.199; frequency of allele chi(2)=1.250, P=0.264). In all subjects, type 2 diabetes mellitus and normal relatives, SUR1-3c/t genotypes were listed (cc: 29.3%, 30.2%, 28.3%; ct: 50.7%, 53.8%, 47.2%; tt: 20%, 16.0%, 24.5% respectively). The frequencies of c were 54.7%, 57.1% and 51.9% respectively. The frequency of c is lower than Han population in northern China. The results show that SUR1 exon16-3c/t polymorphism is not associated with type 2 diabetes mellitus in the population.
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PMID:[Study on the relationship between sulfonylurea receptor 1 gene polymorphism and type 2 diabetes mellitus]. 1562 59

Paraoxonase (PON1) is a serum enzyme with an antioxidant function, protecting the low density lipoproteins (LDL) from oxidative modifications. Because diabetic patients are at greater risk of oxidative stress, we investigated the effect of PON1 55 methione (M)/leucine (L) and PON1 192 glutamine (A)/arginine (B) polymorphisms on oxidant-antioxidant system in 213 individuals with type 2 diabetes mellitus and 116 non-diabetic control subjects from Turkish population were included in the study. Polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine the PON1 genotypes. Thiobarbituric acid reactive substances (TBARS), conjugated dienes levels in the serum and glutathione (GSH) levels in whole blood were measured spectrophotometrically. In both groups PON1 192 AA and PON1 55 MM genotypes had higher TBARS, conjugated dienes levels and lower GSH levels, whereas PON1 192 BB and PON1 55 LL genotypes had lower TBARS, conjugated diene levels and higher GSH level than other genotypes. We thus conclude that PON1 192 BB and PON1 55 LL alleles have protective effect against oxidative stress.
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PMID:Paraoxonase (PON1) 55 and 192 polymorphism and its effects to oxidant-antioxidant system in turkish patients with type 2 diabetes mellitus. 1597 33

Purinergic P2Y-receptor agonists amplify glucose-induced insulin secretion from pancreatic beta-cells, thus offering new opportunities for the treatment of type 2 diabetes. However, little is known about which subtypes of purinergic P2Y receptors are expressed in these cells. The INS-1 beta-cell line is used as a model of pancreatic beta-cells, expressing most of their properties. Therefore, we investigated the expression of different molecular subtypes in this cell line by means of real time Polymerase Chain Reaction and Western blot. We also performed a characterization of the binding of a prototypic purinergic P2Y agonist, Adenosine-5'-O-(1-[(35)S]thiotriphosphate) (ATP-alpha-[(35)S]), to cell membrane homogenates. The molecular analysis evidenced the presence of five different purinergic P2Y receptor subtypes (P2Y(1), P2Y(2), P2Y(4), P2Y(6) and P2Y(12)), which were expressed at similar levels. The Western blot analysis allowed detecting corresponding proteins. The binding assay demonstrated a specific ATP-alpha-[(35)S] interaction on high (40%) and low (60%) affinity components. The analysis of ATP-alpha-[(35)S] pharmacological profile on both sites permitted to classify the high affinity binding site as representative of the purinergic P2Y(1) receptor subtype and the low affinity binding site of the P2Y(4) and/or P2Y(6) receptor subtypes. ATP-alpha-S and Adenosine-5'-O-(2-thiodiphosphate) (ADP-beta-S) exhibited opposite selectivity on high and low affinity binding sites. Although purinergic P2Y(1) receptor, or a P2Y(1)-like subtype, has been generally considered as that implicated in the modulation of glucose-induced insulin release, the present data show that the beta-cell expresses a complex profile of purinergic P2Y receptor subtypes, the functional implication of which remains to be fully elucidated.
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PMID:Expression of purinergic P2Y receptor subtypes by INS-1 insulinoma beta-cells: a molecular and binding characterization. 1750 60

Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and direct sequencing were applied to detect a new point mutation of nt7444G-->A in the mitochondrial DNA in a type 2 diabetes mellitus family. The related clinical data were also collected and analyzed. mtDNA G7444A mutation in the cytochrome c oxidase I (COI) gene was found in 11 of 27 cases, all of whom were from the maternal side. Among them, 5 were confirmed to have type 2 diabetes mellitus, and one had impaired glucose tolerance. We conclude that the novel point mutation of mtDNA G7444A may be an independent factor associated with type 2 diabetes mellitus.
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PMID:[Study on a new point mutation of nt7444 G-->A in the mitochondrial DNA in a type 2 diabetes mellitus family]. 1754 5

In order to assess the importance of HCV infection as a possible risk factor for type 2 diabetes mellitus, a case-control study was conducted, comparing the prevalence of HCV infection among diabetic and non-diabetic patients. Diabetic outpatients attending to a University Hospital in Central-West Brazil were evaluated between April and October 2005. A control group composed by patients from the same institution was matched by gender and age. Candidates to control group were included only if fasting glucose measures were under 100 mg/dL. Diabetics and controls had blood samples taken in order to test for antibodies against HCV (anti-HCV) by enzyme-immunoassay. Polymerase chain reaction and immunoblot were performed to confirm the anti-HCV status. Each group included 206 participants. Despite of the groups were in general comparable. The diabetics had a greater body mass average and smaller family income. The prevalence of confirmed anti-HCV in the diabetic group was of 1.4%, which was similar to the controls (1%). Finding statistical difference may have been hampered by the low frequency of HCV infection in both groups. It was not possible to demonstrate a role of HCV as an etiologic factor in type 2 diabetes, since HCV infected patients represented a small portion of the overall diabetes cases. This finding does not allow to recommend regular screening for HCV infection in type 2 diabetics in this region.
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PMID:Hepatitis C as a risk factor for diabetes type 2: lack of evidence in a hospital in central-west Brazil. 1855 10


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