Navegando por Palavras-chave "CYP27B1"

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    Avaliação da expressão do receptor de vitamina d (VDR) e das hidroxilases CYP27B1 e CYP24A1 e concentração sérica de 1,25-dihidroxivitamina D em pacientes litiásicos
    (Universidade Federal de São Paulo (UNIFESP), 2019-06-03) Melo, Thalita Lima [UNIFESP]; Heilberg, Ita Pfeferman [UNIFESP]; http://lattes.cnpq.br/5039409992847018; http://lattes.cnpq.br/0399585291142239; Universidade Federal de São Paulo (UNIFESP)
    Introduction: The pathophysiological mechanisms for hypercalciuria comprise increased intestinal calcium absorption, reduced renal tubular reabsorption and increased bone resorption, which are influenced by calciotropic hormones such as PTH, FGF-23, 25OHD and 1,25(OH)D. The 1,25(OH)D is synthesized from 25(OH)D by the enzyme CYP27B1 (1α-hydroxylase), exerts its biological functions through binding to the vitamin D receptor (VDR) and is degraded by the enzyme CYP24A1. The expression of VDR and levels of 1,25(OH)D exceed the values of controls in some but not all hypercalciuric stone formers. Objective: We aimed to evaluate the expression of VDR, CYP27B1 and CYP24A1, and the serum 1,25(OH)D levels in hypercalciuric stone formers (HSF) in comparison with normocalciuric stone formers (NSF) and healthy subjects as controls (HS). Methods: Twenty-four-hour urine collections, blood samples for determination of biochemical and hormonal parameters including Klotho and FGF-23 and a 3-day dietary record were obtained from 30 participants from each of the groups. All participants were paired by gender, age and body mass index. VDR, CYP27B1 and CYP24A1 expression were measured by flow cytometry. Results: HSF compared to NSF and HS presented significantly higher urinary volume (2021±101 vs 1547±101 and 1488±101 ml/24h, p=0.000, mean ± standard error) and higher urinary excretion of calcium (345±12 vs 166±12 and 149±12 mg/24h, p=0.000), sodium (215±12 vs 168±10 and 179±10 mEq/24h, p=0.006), magnesium (108.5±6.8 vs 72.8±6.6 and 82.1±6.7 mg/24h, p=0.001), oxalate (25.3±1.6 vs 21.0±1.6 and 19.7±1.5 mg/24h, p=0.03), uric acid (690±26 vs 572±26 and 556±26 mg/24h, p=0.000) and phosphorus (979±49 vs 791±48 and 702±49 mg/24h, p=0.000). Calcium intake was lower in HSF versus NSF and HS (442±41 vs 594±42 and 559±41mg, respectively, p=0.027) and salt (NaCl) intake was higher in HSF versus NSF and HS (12.6±0.6 vs 9.8±0.6 e 10.5±0.6 g/day, p=0.006). Protein intake, assessed by protein equivalent of nitrogen appearance (PNA), was lower in HSF and NSF versus HS (1.1±0.0 and 1.0±0.0 vs 1.4±0.0 g/kg/day, p=0.006) with no differences in estimated potential renal acid load (PRAL), phosphorus and potassium intake among groups. Ionized calcium was significantly lower in HSF than NSF (1.29±0.0 vs 1.31±0.0 mmol/L, p<0.01). Serum 1,25(OH)D was significantly higher, even within normal ranges, in HSF and NSF than HS (22.5±1.2; 22.2±1.2 vs 17.4±1.2 pg/ml, p=0.007, respectively) but serum 25(OH)D, PTH, α-Klotho and plasma FGF-23 did not differ among groups. The VDR expression was higher in HSF and NSF than HS (80.8±3.2; 78.7±3.3 vs 68.6±3.2%, p=0.023). Although CYP27B1 and CYP24A1 expressions were similar among all groups, the ratio 1,25(OH)D/CYP24A1 was higher in HSF and NSF than in HS (1.43±0.25 and 0.56±0.10 than 0.34±0.06, p=0.00). Conclusions: Stone-formers, regardless of urinary calcium levels, had higher VDR expression and 1,25(OH)D levels compared to controls. Higher 1,25(OH)D/CYP24A1 ratio suggested a lower degradation of 1,25(OH)D by CYP24A1 in HSF and NSF.
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    Genetic polymorphisms of vitamin D metabolism genes and serum level of vitamin D in colorectal cancer
    (Wichtig Publishing, 2017) Vidigal, Veronica Marques [UNIFESP]; Nazareth Aguiar Junior, Pedro [UNIFESP]; Silva, Tiago Donizetti [UNIFESP]; de Oliveira, Juliana [UNIFESP]; Marques Pimenta, Celia Aparecida [UNIFESP]; Felipe, Aledson Vitor [UNIFESP]; Forones, Nora Manoukian [UNIFESP]
    Background: The metabolism of vitamin D is complex, its receptor (VDR) and proteins encoded by the genes CYP27B2 and CYP24A1 can influence vitamin D serum levels. The aim of this study was to investigate the relationship of the polymorphisms of VDR (ApaI and BsmI), CYP27B1 and CYP24A1 with serum vitamin D levels in both forms, 25(OH)D-3 (circulating form) and 1,25(OH)(2)D-3 (active form), in colorectal cancer (CRC) patients. Methods: One hundred fifty-two CRC patients and 321 controls were included. DNA was extracted from peripheral blood. Polymorphisms of BsmI and ApaI were identified by PCR-RFLP. Those of CYP24A1 (rs6013897, rs158552 and rs17217119) and CYP27B1 (rs10877012) were determined by gene sequencing. Results: The median serum levels of circulating vitamin D were not different between CRC patients and controls
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    Genetic polymorphisms of vitamin D receptor (VDR), CYP27B1 and CYP24A1 genes and the risk of colorectal cancer
    (Wichtig Publishing, 2017) Vidigal, Veronica Marques [UNIFESP]; Silva, Tiago Donizetti [UNIFESP]; de Oliveira, Juliana [UNIFESP]; Marques Pimenta, Celia Aparecida [UNIFESP]; Felipe, Aledson Vitor [UNIFESP]; Forones, Nora Manoukian [UNIFESP]
    Introduction: Vitamin D receptor (VDR) and proteins encoded by the genes CYP27B2 and CYP24A1 involved in the production and inactivation of vitamin D can influence vitamin D and the susceptibility to colorectal cancer (CRC). The objective of this study was to investigate the relationship between the risk of CRC and polymorphisms in VDR, CYP27B1 and CYP24A1, lifestyle and dietary habits. Methods: The study included 152 patients with CRC and 321 controls. All participants answered a questionnaire on their dietary habits, alcohol consumption and smoking habits. DNA was extracted from peripheral blood. Polymorphisms of BsmI and ApaI were identified by performing PCR-RFLP. Identification of CYP24A1 (rs6013897, rs158552 and rs17217119) and CYP27B1 (rs10877012) polymorphisms was performed by gene sequencing. Results: Smoking, alcohol use, and low or no consumption of fruit, cereals and dairy products were associated with an increased risk of CRC. A heterozygous genotype Aa or an association genotype aa + Aa of the VDR ApaI polymorphism increased the risk of CRC. The VDR BsmI polymorphism was not significantly associated with the risk of CRC. Multivariate analysis showed that heterozygous and association genotype AT + AA of the rs6013897 polymorphism, genotype CT of the rs158552 polymorphism, association genotype CT + CC and genotypes AA and GG of the rs17217119 polymorphism of CYP24A1, and heterozygous genotype GT and association genotype GT + TT of the rs10877012 polymorphism in CYP27B1 were associated with a higher risk of CRC. Conclusions: Dietary habits, lifestyle, and polymorphisms in VDR (ApaI), CYP24A1 (rs6013897, rs158552, rs17217119) and CYP27B1 (rs10877012) were associated with a higher risk of CRC.