Rubello Domenico, Giannini Sandro, D'Angelo Angela, Nobile Martino, Carraio Gianni, Rigotti Paolo, Marchini Francesco, Zaninotto Martina, Dalle Carbonare Luca, Sartori Leonardo, Nibale Otello, Carpi Angelo
Service of Nuclear Medicine, S. Maria della Misericordia Rovigo Hospital, Istituto Oncologico Veneto, Viale Tre Martiri, 140, I-45100 Rovigo, Italy.
Biomed Pharmacother. 2005 Aug;59(7):402-7. doi: 10.1016/j.biopha.2004.09.015.
Immunosuppresive treatment and secondary hyperparathyroidism (SHPT) are considered among the most important pathogenetic factors for post-renal transplant bone disease. The aim of this study was to investigate the relationships among vitamin D receptor (VDR) gene polymorphism, parathyroid hormone (PTH) levels and bone density in renal transplant recipients. We enrolled 75 patients (50 male and 25 female, mean age 47+/-11 years) who had undergone kidney transplantation 53+/-4 months before. All patients underwent an evaluation of the main biochemical parameters of bone metabolism as well bone densitometry. VDR alleles were typed by a PCR assay based on a polymorphic BsmI restriction site. When patients were categorized according to the VDR genotype (BB, Bb, bb), serum creatinine and the cumulative doses of immunosuppressive drugs were similar across the groups. PTH levels higher than 80 pg/ml were found in 53.6% of the patients, with the highest values being detected in the bb VDR genotype (P<0.05). PTH was significantly correlated to urinary NTx values. Bone density was low in the whole population; however, spinal bone density was lower in the bb subgroup (P<0.02). In the whole population, only PTH (P<0.05) and body mass index (P<0.01) were independent predictors of spinal bone density. Grouping patients by the VDR gene polymorphism, only PTH continued to be an independent predictor of spinal bone density in the bb allele subgroup (R(2) Adj.=0.17). We can conclude that the VDR genotype polymorphism affects bone density of renal transplant recipients via its effects on the severity of SHPT.
免疫抑制治疗和继发性甲状旁腺功能亢进(SHPT)被认为是肾移植后骨病最重要的发病因素。本研究的目的是探讨肾移植受者中维生素D受体(VDR)基因多态性、甲状旁腺激素(PTH)水平与骨密度之间的关系。我们纳入了75例患者(50例男性和25例女性,平均年龄47±11岁),这些患者在53±4个月前接受了肾移植。所有患者均接受了骨代谢主要生化参数以及骨密度测定的评估。通过基于多态性BsmI限制性位点的PCR检测对VDR等位基因进行分型。当根据VDR基因型(BB、Bb、bb)对患者进行分类时,各组间血清肌酐和免疫抑制药物的累积剂量相似。53.6%的患者PTH水平高于80 pg/ml,其中bb VDR基因型患者的PTH水平最高(P<0.05)。PTH与尿NTx值显著相关。总体人群骨密度较低;然而,bb亚组的脊柱骨密度更低(P<0.02)。在总体人群中,只有PTH(P<0.05)和体重指数(P<0.01)是脊柱骨密度的独立预测因素。根据VDR基因多态性对患者进行分组,在bb等位基因亚组中,只有PTH仍然是脊柱骨密度的独立预测因素(校正R²=0.17)。我们可以得出结论,VDR基因型多态性通过影响SHPT的严重程度来影响肾移植受者的骨密度。