维生素D受体基因Bsm Ⅰ位点多态性对维持性血液透析患者骨代谢的影响

Effects of Vitamin D Receptor Gene BsmⅠ Polymorphism on Renal Osteodystropy in Hemodialysis Patients

目的:探讨维生素D受体(VDR)BsmⅠ基因多态性对湖北地区汉族人群维持性血液透析(MHD)患者骨代谢的影响。方法:记录120例MHD患者一般临床资料和临床常用血生化指标;双能X线吸收测定法测定患者桡骨骨密度;聚合酶链反应-限制性片断长度多态性(PCR-RFLP)技术检测BsmⅠ基因型和等位基因频率;ELISA法测定血清25-(OH)D3水平。结果:MHD患者BB基因型2.5%,Bb基因型31.7%,bb基因型65.8%,B等位基因频率18.4%,b等位基因频率81.6%。BB+Bb基因型患者全段甲状旁腺激素(iPTH)和碱性磷酸酶(ALP)水平明显升高,桡骨骨密度显著下降,与bb型比较差异有统计学意义(P<0.05);与iPTH<150pg/ml组比较,BB+Bb基因型频率在iPTH 300-600pg/ml组显著升高(χ2=10.81,P<0.005);iPTH 300-600pg/ml组B等位基因频率显著上升,与iPTH<150pg/ml组和iPTH 150-300pg/ml组比较差异有统计学意义(χ2=11.43,χ2=7.11,P<0.01)。B等位基因与iPTH(r=0.47,P<0.05)和ALP(r=0.52,P<0.05)显著正相关,与桡骨骨密度(r=-0.36,P<0.05)显著负相关。结论:B等位基因可能为湖北汉族MHD患者遗传易感基因,通过改变VDR敏感性或影响甲状旁腺功能导致透析患者发生骨代谢异常。

Objective：To explore the effects of vitamin D receptor gene BsmⅠ polymorphism on renal osteodystropy in Hubei Hannational maintenance hemodialysis（MHD）patients.Methods：Clinical data and routine biochemical parameters of 120 patients with maintenance hemodialysis were analyzed,bone mineral density of radius were performed by dual energy X-ray absorptiometry,the genotype and allele frequency of BsmⅠ were tested by polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP）,and the level of 25-（OH）D3were detected by Enzyme linked immunosorbent assay.Results：The polymorphism percentages in MHD patients were BB/Bb/bb：2.5%/31.7%/65.8%,and the B/b allele frequency were 18.4% and 81.6%.The level of iPTH and alkaline phosphatase increased significantly and the bone mineral density of radius decreased significantly in MHD patients with BB and Bb genotype than with bb geno-type.Patients in iPTH 300-600pg/ml group had significantly higher BB and Bb genotype frequency and B allele frequency than in iPTH150pg/ml group and in iPTH 300-600pg/ml group（χ2=10.81,14.76,11.43,7.11,P〈0.01）.The number of B alleles was positively correlated with iPTH（r=0.47,P〈0.05）and ALP（r=0.52,P〈0.05）,and negatively correlated with bone mineral density of radius（r=-0.36,P〈0.05）.Conclusion：It is suggested that B alleles of the BsmⅠ polymorphism could be considered as a genetic susceptibility gene in Hubei Han national MHD patients with renal osteodystropy,maybe through the impact on vitamin D signaling pathway or parathyroid function.