Bouksila Mouna, Kaabachi Wajih, Mrad Mehdi, Smaoui Wided, El Kateb Elhem Cheour, Zouaghi Mohammed Karim, Hamzaoui Kamel, Bahlous Afef
Immuno-Rheumatology Research Laboratory, Rheumatology Department, La Rabta Hospital, University of Tunis-El Manar, Tunis, Tunisia; Laboratory of Clinical Biochemistry and Hormonology, Pasteur Institute of Tunis, Tunis El Manar University, Tunisia.
Department of Basic Sciences, Unit Research 12SP15 "Homeostasis and Cell Dysfunction", Medicine School of Tunis, Tunis El Manar University, Tunis 1007, Tunisia.
Clin Biochem. 2018 Apr;54:42-50. doi: 10.1016/j.clinbiochem.2018.02.009. Epub 2018 Feb 16.
The aim of this study was to evaluate the association between two VDR SNPs FokI and BsmI and mineral status in ESRD patients.
Our case-control study included 100 patients with chronic renal failure in ESRD and 149 healthy subjects. We measured the serum Vitamin D levels and the serum intact PTH level by Electrochemiluminescence Technology (cobas E411 analyzer). We evaluated the serum FGF23 levels by indirect ELISA method. The genotyping of two VDR gene variants FokI and BsmI was carried out by PCR-RFLP technique.
In our study, the FokI TT genotype was associated with lower risk of ESRD development (OR = 0.176, Padj = 0.039). The difference in PTH and FGF23 levels between cases and controls was statistically significant. The expression of FokI CT genotype in subjects with diabetic nephropathy was associated with a negative correlation between VD and PTH levels (r = -0.620, P = 0.032) and a positive correlation between VD and FGF23 levels (r = 0.967, P = 0.012). A significant differences in VD levels between patients and controls was observed in the presence of FokI TT (P = 0.044) and CT (P = 0.036) genotypes. The expression of FGF23 serum level was significantly elevated in patients than in controls in the presence of the FokI CC and BsmI AG genotypes.
In conclusion, our study shows the existence of an association between VDR FokI, BsmI polymorphisms and mineral status in ESRD patients. The presence of VDR variants affect the protein expression of VD, phosphorus, FGF23 and PTH.
本研究旨在评估维生素D受体（VDR）的两个单核苷酸多态性（SNP）FokI和BsmI与终末期肾病（ESRD）患者矿物质状态之间的关联。
我们的病例对照研究纳入了100例ESRD慢性肾衰竭患者和149名健康受试者。我们采用电化学发光技术（cobas E411分析仪）测量血清维生素D水平和血清完整甲状旁腺激素（PTH）水平。我们通过间接酶联免疫吸附测定（ELISA）法评估血清成纤维细胞生长因子23（FGF23）水平。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术对VDR基因的两个变体FokI和BsmI进行基因分型。
在我们的研究中，FokI TT基因型与ESRD发生风险较低相关（比值比[OR]=0.176，校正P值[Padj]=0.039）。病例组和对照组之间PTH和FGF23水平的差异具有统计学意义。糖尿病肾病患者中FokI CT基因型的表达与维生素D（VD）和PTH水平呈负相关（r=-0.620，P=0.032），与VD和FGF23水平呈正相关（r=0.967，P=0.012）。在存在FokI TT（P=0.044）和CT（P=0.036）基因型的情况下，观察到患者和对照组之间的VD水平存在显著差异。在存在FokI CC和BsmI AG基因型的情况下，患者的FGF23血清水平表达显著高于对照组。
总之，我们的研究表明VDR FokI、BsmI多态性与ESRD患者矿物质状态之间存在关联。VDR变体的存在影响VD、磷、FGF23和PTH的蛋白表达。
