Expression of vitamin D receptor, CYP27B1 and CYP24A1 hydroxylases and 1,25-dihydroxyvitamin D3 levels in stone formers

Expression of vitamin D receptor, CYP27B1 and CYP24A1 hydroxylases and 1,25-dihydroxyvitamin D3 levels in stone formers
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DOI:
10.1007/s00240-019-01163-9
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发表时间:
2019-11-06
期刊:
影响因子:
3.1
通讯作者:
Heilberg, Ita Pfeferman
Heilberg, Ita Pfeferman
中科院分区:
医学2区
文献类型:
--
作者:
Melo, Thalita Lima;Goncalves Esper, Priscila Ligeiro;Heilberg, Ita Pfeferman

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维生素D受体(VDR)和1,25-二羟维生素D-3 [1,25(OH)D]水平的表达在一些但不是所有的高钙尿石形成者(HSF)中超过对照值。我们的目的是评估血清1,25(OH)D水平,VDR,CYP27 B1和CYP24 A1羟化酶的表达在HSF与正常钙尿结石形成者(NSF)和健康受试者(HS)进行比较。从每组30名参与者中获得血液样本,24小时尿液收集和3天饮食记录。通过流式细胞术测量VDR、CYP27 B1和CYP24 A1的表达。HSF的尿量、钠、镁、草酸、尿酸和磷显著高于NSF和HS。HSF的钙摄入量低于NSF和HS(分别为442 +/-41 vs 594 +/-42和559 +/-41 mg/天,p = 0.027)。HSF的离子钙显著低于NSF(1.29 +/-0.0 vs 1.31 +/-0.0 mmol/L,p <0.01)。HSF和NSF的血清1,25(OH)D显著高于HS(22.5 +/-1.2; 22.2 +/-1.2 vs 17.4 +/-1.2 pg/ml,p = 0.007),但血清25(OH)D、PTH、klotho和血浆FGF-23在组间无差异。HSF和NSF中VDR表达高于HS(80.8 +/-3.2; 78.7 +/-3.3 vs 68.6 +/-3.2%,p = 0.023)。尽管所有组中的CYP27 B1和CYP24 A1表达相似,但HSF和NSF中的1,25(OH)D/CYP24 A1比值高于HS(1.43 +/-0.25和0.56 +/-0.10 vs 0.34 +/-0.06,p = 0.00)。无论尿钙排泄如何,结石患者的VDR表达和1,25(OH)D水平均高于HS,即使在正常范围内。较高的1,25(OH)D/CYP24A1比值表明HSF和NSF中CYP24A1对1,25(OH)D的降解较低。
The expression of vitamin D receptor (VDR) and 1,25-dihydroxyvitamin D-3 [1,25(OH)D] levels exceed the values of controls in some but not all hypercalciuric stone formers (HSF). We aimed to evaluate serum 1,25(OH)D levels, the expression of VDR, CYP27B1, and CYP24A1 hydroxylases in HSF in comparison with normocalciuric stone formers (NSF) and healthy subjects (HS). Blood samples, 24-h urine collections and a 3-day dietary record were obtained from 30 participants from each of the groups. The expression of VDR, CYP27B1, and CYP24A1 was measured by flow cytometry. HSF presented significantly higher urinary volume, sodium, magnesium, oxalate, uric acid, and phosphorus than NSF and HS. Calcium intake was lower in HSF versus NSF and HS (442 +/- 41 vs 594 +/- 42 and 559 +/- 41 mg/day, respectively, p = 0.027). 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 in HSF and NSF than HS (22.5 +/- 1.2; 22.2 +/- 1.2 vs 17.4 +/- 1.2 pg/ml, p = 0.007) but serum 25(OH)D, PTH, klotho and plasma FGF-23 did not differ between groups. 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 of 1,25(OH)D/CYP24A1 was higher in HSF and NSF than in HS (1.43 +/- 0.25 and 0.56 +/- 0.10 vs 0.34 +/- 0.06, p = 0.00). Stone formers, regardless of urinary calcium excretion, had higher VDR expression and 1,25(OH)D levels than HS, even in ranges considered normal. Higher 1,25(OH)D/CYP24A1 ratio suggested a lower degradation of 1,25(OH)D by CYP24A1 in HSF and NSF.