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Taq1B CETP Polymorphism and Cardiovascular Risk in an Endogamous Pop-ulation of Diabetic Men: A Study in Santa Rosa Del Conlara, San Luis, Argentina

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Journal of Diabetes Mellitus 2015年第2期5卷 123-134页

作者： susana siewert Irma Gonzalez Sergio Filipuzzi Dario C. Ramirez Marta S. Ojeda Laboratory of Diabetes Department of Biochemistry and Biological Sciences School of Chemistry Biochemistry and Pharmacy National University of San Luis San Luis Argentina Hospital of Santa Rosa Government of the Province of San Luis Santa Rosa del Conlara Argentina Laboratory of Experimental Medicine and Therapeutics IMIBIO-SL-National Bureau of Science and Technology (CONICET) & National University of San Luis San Luis Argentina

Objectives: Type 2 diabetes mellitus (T2DM) patients are at increased risk of cardiovascular diseases (CVDs). Several polymorphisms in the cholesterol ester transfer protein (CETP) gene have been reported. The aim of this study was to determine the distribution and effect of the Taq1B polymorphism in the CETP gene on clinical and biochemical indicators of CVD risk in a population of endogamous-T2DM men. Methods: 102 men (57.5 ± 9.3 years old) inhabitants of Santa Rosa del Conlara, San Luis, Argentina, were recruited and assigned into two groups (22 control and 80 T2DM). Further, these two groups were subdivided according to their Taq1B CETP gene genotypes (i.e., B1B1, B1B2 and B2B2). Clinical and fasting-plasma biochemical indicators of CVD risk were measured and their association with the B1 allele was determined. Results: Compared to control, T2DM men had more central obesity, hypertension, atherogenic index, insulin resistance and poorly controlled diabetes. Compared to T2DM men having the B2 allele, those T2DM men having the B1 allele have increased risk of CVD as assessed by systolic blood pressure (156 ± 16.0 vs 135.8 ± 19.2, p = 0.015), atherogenic index (6.15 ± 1.3 vs 4.4 ± 0.7, p = 0.0008), HDL-c levels (38.9 ± 5.3 vs 64.4 ± 8.2, p ± 3.0 vs 2.4 ± 0.78, p = 0.004). Interestingly, only body mass index (r = ﹣0.559, p = 0.01) and HDL-c concentration (r = ﹣0.492, p = 0.02) negatively correlated with CVD risk in the endogamous population of B1B1 and B1B2 T2DM men. Conclusion: The B1 allele of the CETP gene predicts cardiovascular complications in an endogamous population of T2DM men.

关键词： Cholesteryl Ester Transfer Protein Taq1B Polymorphism Endogamous Type 2 Diabetic Men Cardiovascular Disease Risk Santa Rosa del Conlara-San Luis-Argentina

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Downregulation of Nrf2 and HO-1 expression contributes to oxidative stress in type 2 diabetes mellitus: A study in Juana Koslay City, San Luis, Argentina

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Journal of Diabetes Mellitus 2013年第2期3卷 71-78页

作者： susana siewert Irma González Lucas Santillán Roberto Lucero Marta S. Ojeda María S. Gimenez Juana Koslay Regional Center Ministry of Health of the Province of San Luis San Luis Argentina Laboratory of Diabetes Department of Biochemistry and Biological Sciences School of ChemistryBiochemistry and Pharmacy National University of San Luis San Luis Argentina Laboratory of Pathological & Biological Chemistry National University of San Luis & IMIBIO-SL-National Bureau of Science and Technology (CONICET) San Luis Argentina

Oxidative stress is associated with diabetes mellitus, a condition characterized by increased prevalence and progression rate of cardiovascular disease. NFE2-related factor 2 (Nrf2) is a master regulator of cellular detoxification responses and redox status. The aim of this study was to examine associations between type 2 Diabetes Mellitus (T2DM), oxidative stress and the expression of NFE2-related factor 2 (Nrf2) in a population of diabetic patients living in Juana Koslay City, San Luis, Argentina. In addition, we evaluated the functional relevance of Nrf2 by measuring the HO-1 expression among persons with type 2 diabetes. We measured clinical and biochemical parameters related to lipid metabolism and oxidative stress in a population of Type 2 Diabetes Mellitus patients (T2DM, n = 40) and controls (Co, n = 30). Compared to Co, T2DM patients had higher fasting serum glucose, glycated hemoglobin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and thiobarbituric acid reactive substances and lower high-density lipoprotein cholesterol. T2DM individuals had also higher atherogenic index and body mass index than controls. We also founded that HO-1 mRNA in whole blood was lower in T2DM than controls, suggesting that T2DM may have an altered antioxidant response to oxidative stress. Interestingly, we found reduced Nrf2 mRNA in whole blood from T2DM compared to Co. The results from this study provide novel evidence that genes associated to antioxidant defense mechanisms are markedly reduced in patients with type 2 diabetes, and that the reduction in the expression of these genes could be associated to hyperglycemia and increased levels of MDA. Linear regression analysis revealed that there was a strong and positive correlation between the changes of Nrf2 and HO-1 expression levels.

关键词： Type 2 Diabetes Mellitus HO-1 Nrf2 and TBAR’S

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Hyperglycemia promotes overexpression of SR-BII isoform of the scavenger receptor class B type I in type 2 diabetes mellitus: A study in Juana Koslay City, San Luis, Argentina

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Journal of Diabetes Mellitus 2013年第4期3卷 172-183页

作者： Gisela V. Mendoza susana siewert Irma González María C. Della Vedova Gustavo Fernandez Marta S. Ojeda Laboratory of Diabetes Department of Biochemistry and Biological Sciences School of Chemistry Biochemistry and Pharmacy National University of San Luis San Luis Argentina

The scavenger receptor class B type I (SR-BI) is a high-density lipoprotein (HDL) receptor involved in reverse cholesterol transport. Some studies reported the association to be stronger in the presence of diabetes. The full length gene encoding SR-BI is comprised in 13 exons that are alternatively spliced to produce two major transcripts: the full length SR-BI and the splice variant SR-BII, in which exon 12 is skipped. Considering that type 2 diabetes status is characterized by changes in the concentration of plasma lipids, modifications in lipoprotein size and composition, which may be important modulators of the SR-BI expression;the aims of the study were to examine the influence of SR-BI polymorphism (rs838895) on lipid profile and SR-BI mRNA expression in a population of diabetic patients living in Juana Koslay City. Blood samples were drawn from controls (n = 40) and Type 2 diabetic patients (n = 66) and DNA and total RNA were obtained. SR-BI mRNA expression was measured by RT-PCR and SR-BI polymorphism was detected by Tetra Primer ARMSPCR. Compared to controls, diabetic patients had higher fasting serum glucose, glycated hemoglobin, triglycerides, total cholesterol, lowdensity lipoprotein cholesterol, and lower highdensity lipoprotein cholesterol. SR-BI mRNA expression was lower in T2DM when compared to controls, suggesting that the hyperglycemia presents in T2DM patients down-regulates SR-BI mRNA expression. Interestingly, we found that decreased SR-BI expression resulted in markedly increased plasma LDL concentrations in T2DM subjects, and the overexpression of SRBII isoform is responsible for the markedly increased plasma LDL-c concentrations. The polymorphism (rs838895) did not modify the mRNA level of SR-BI in leucocytes from control and diabetic patients. This study provides novel evidence suggesting that hyperglycemia may affect reverse cholesterol transport by controlling SRBI expression in diabetic patients. LDL cholesterol levels are associated with

关键词： Type 2 Diabetes Mellitus Hyperglycemia Scavenger Receptor Class B Type I and Polymorphism

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