Publications (18) View all
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Dataset: Oxidative Metabolism of neutrophils
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Article: Relationship of short tandem repeats flanking leptin-melanocortin pathway genes with anthropometric profile and leptinemia in Brazilian individuals.
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ABSTRACT: To investigate the relationship of short tandem repeats (STR) near genes involved in the leptin-melanocortin pathway with body mass index (BMI) and leptinemia. Anthropometric variables and leptinemia were measured in 100 obese and 110 nonobese individuals. D1S200, D2S1788, DS11912, and D18S858 loci were analyzed by PCR and high-resolution electrophoresis. Overall STR allele frequencies were similar between the obese and non-obese group (p > 0.05). Individual alleles D1S200 (17), D11S912 (43), D18S858 (11/12) were associated with obesity (p < 0.05). Individuals carrying these alleles showed higher BMI than non-carriers (p < 0.05). Moreover, a relationship between D18S858 11/12 alleles and increased waist circumference was found (p = 0.040). On the other hand, leptinemia was not influenced by the studied STRs (p > 0.05). D1S200, D11S912, and D18S858 loci are associated with increased BMI and risk for obesity in this sample.Arquivos brasileiros de endocrinologia e metabologia 02/2012; 56(1):47-53. · 0.68 Impact Factor -
Article: Influence of polymorphisms and cholesterol-lowering treatment on SCARB1 mRNA expression.
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ABSTRACT: This study evaluated the influence of polymorphisms and cholesterol-lowering treatments on SCARB1 mRNA expression in peripheral blood mononuclear cells and in HepG2 and Caco-2 cells. Blood samples were drawn from normolipidemic (NL, n = 166) and hypercholesterolemic (HC, n = 123) individuals to extract DNA and total RNA and to analyze the lipid profile. After a 4-week washout period, 98 HC individuals were treated with atorvastatin (10 mg/day/4 weeks) whereas 25 were treated with ezetimibe (10 mg/day/4 weeks), followed by simvastatin (10 mg/day/8 weeks) and simvastatin plus ezetimibe (10 mg each/day/4 weeks). HepG2 and Caco-2 cells were treated with atorvastatin, simvastatin and ezetimibe at various concentrations for 12 and 24 h and collected for RNA extraction. SCARB1 mRNA expression was measured by TaqMan® assay and SCARB1 c.4G> A, c.726 + 54C> T and c.1080C> T polymorphisms were detected by PCR-RFLP. High LDL cholesterol (> 160 mg/dL) values were associated with low baseline SCARB1 mRNA expression in PBMC. Allele T carriers for SCARB1 c.726+54C> T had lower basal SCARB1 transcription in PBMC (p < 0.05). Simvastatin, atorvastatin and ezetimibe treatments did not modify the SCARB1 mRNA level in PBMC from HC patients. Similarly, these cholesterol-lowering drugs did not modulate the SCARB1 expression in HepG2 and Caco-2 cells in spite of the concentration and time of exposure (p > 0.05). LDL cholesterol levels and SCARB1 c.726 + 54C> T are associated with low mRNA expression in mononuclear cells. Cholesterol-lowering drugs do not modulate SCARB1 expression in PBMC from HC subjects or in HepG2 and Caco-2 cells.Journal of atherosclerosis and thrombosis 04/2011; 18(8):640-51. · 2.69 Impact Factor -
Article: Effects of lipid-lowering drugs on reverse cholesterol transport gene expressions in peripheral blood mononuclear and HepG2 cells.
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ABSTRACT: The ATP-binding cassette transporters, ABCA1 and ABCG1, are LXR-target genes that play an important role in reverse cholesterol transport. We examined the effects of inhibitors of the cholesterol absorption (ezetimibe) and synthesis (statins) on expression of these transporters in HepG2 cells and peripheral blood mononuclear cells (PBMCs) of individuals with primary (and nonfamilial) hypercholesterolemia (HC). A total of 48 HC individuals were treated with atorvastatin (10 mg/day/4 weeks) and 23 were treated with ezetimibe (10 mg/day/4 weeks), followed by simvastatin (10 mg/day/8 weeks) and simvastatin plus ezetimibe (10 mg of each/day/4 weeks). Gene expression was examined in statin- or ezetimibe-treated and control HepG2 cells as well as PBMCs using real-time PCR. Results: In PBMCs, statins and ezetimibe downregulated ABCA1 and ABCG1 mRNA expression but did not modulate NR1H2 (LXR-β) and NR1H3 (LXR-α) levels. Positive correlations of ABCA1 with ABCG1 and of NR1H2 with NR1H3 expressions were found in all phases of the treatments. In HepG2 cells, ABCA1 mRNA levels remained unaltered while ABCG1 expression was increased by statin (1.0-10.0 µM) or ezetimibe (5.0 µM) treatments. Atorvastatin upregulated NR1H2 and NR1H3 only at 10.0 µM, meanwhile ezetimibe (1.0-5.0 µM) downregulated NR1H2 but did not change NR1H3 expression. Our findings reveal that lipid-lowering drugs downregulate ABCA1 and ABCG1 mRNA expression in PBMCs of HC individuals and exhibit differential effects on HepG2 cells. Moreover, they indicate that the ABCA1 and ABCG1 transcript levels were not correlated directly to LXR mRNA expression in both cell models treated with lipid-lowering drugs.Pharmacogenomics 09/2010; 11(9):1235-46. · 3.97 Impact Factor -
Article: Relationship between variants of the leptin gene and obesity and metabolic biomarkers in Brazilian individuals.
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ABSTRACT: The relationship between variants of the leptin gene (LEP) and obesity and metabolic biomarkers was investigated in Brazilian individuals. One-hundred-ten obese (BMI > 30 kg/m(2)) and 100 non-obese individuals (145 women and 65 men, aged 49 +/- 14 years) were randomly selected. Plasma leptin, glycemia, serum lipid measurements and LEP -2548G>A and 3'HVR polymorphisms were analyzed. The LEP -2548GG genotype was associated with a 2.2% and 2.0% increase in BMI (p = 0.009) and plasma leptin (p = 0.031), respectively. 3'HVR I/II (classes I/I+I/II) genotypes contributed with 1.8% of BMI values (p = 0.046). LEP I/G combined genotypes (I/IGG, I/IGA and I/IIGG) were associated with obesity, and increased BMI, waist circumference, leptin and triglycerides (p < 0.05). These relationships were found in women (p < 0.05) but not in men. LEP I/G combined genotypes were not associated with hypertension, hyperglycemia, dyslipidemia and coronary artery disease. LEP I/G combined genotypes are associated with obesity-related metabolic biomarkers and phenotype in a gender-dependent manner.Arquivos brasileiros de endocrinologia e metabologia 03/2010; 54(3):282-8. · 0.68 Impact Factor
