海南医科大学学报

目的:探讨维生素D受体基因多态性与终末期肾病透析患者预后的关系。方法:收集2016年1月～2016年6月在我院行规律血液透析的终末期肾病(end-stage renal disease, ESRD)患者80例,同期收集来我院体检健康的志愿者80例作为对照组。通过提取研究对象外周血DNA进行扩增和特异性酶切鉴定维生素D受体基因rs1544410(BsmI)位点的多态性,包括野生型GG(bb)和突变型GA(Bb)、AA(BB)3种。分析比较BsmI在终末期肾病患者和正常志愿者中的分布差异,进一步分析BsmI位点与终末期肾病患者相关临床特征的相关性,根据患者随访结果分析BsmI位点与终末期肾病患者预后的关系。结果:终末期肾病患者维生素D受体BsmI位点野生型(bb)发生率明显低于对照组,而突变型(Bb和BB)发生率高于对照组,优势比为1.378(P=0.004)。BsmI位点的等位基因碱基频率发现终末期肾病患者A碱基发生率高于对照组,优势比1.368(P=0.01)。终末期肾病患者BsmI位点基因型和临床特征比较,发现不同基因型患者无年龄、男女性别比、BMI、高血压、糖尿病、低密度脂蛋白、高密度脂蛋白、甘油三酯、尿素氮、血肌酐、血钙、血磷、血清白蛋白、血清维生素D水平等相关指标差异。bb组治疗1年后生存率明显高于Bb组和BB组(P=0.003 6)。K-M生存分析表明bb组中位生存时间20个月,Bb组中位生存时间8个月,BB组中位生存时间4个月(P=0.000 2)。结论:终末期肾病患者存在较高的BsmI位点突变率(GA、AA型),即碱基G突变为A的发生率较高,且发生突变患者生存时间显著缩短。

Objective: To investigate the relationship between vitamin D receptor gene polymorphism and prognosis in patients with end-stage renal disease undergoing dialysis. Methods:A total of 80 patients with end-stage renal disease(ESRD) who underwent regular hemodialysis in our hospital were admitted from January 2016 to June 2016, and 80 healthy volunteers from our hospital were collected as control group during the same period. The polymorphism of vitamin D receptor gene rs1544410(BsmI) was identified by amplification and specific digestion of peripheral blood DNA, including wild type GG(bb) and mutant GA(Bb) and AA(BB). Thenanalysis and comparisonof the distribution of BsmI in patients with end-stage renal disease and normal volunteers, the correlation between BsmI locus and clinical characteristics of patients with end-stage renal disease, and furtherly analyze the relationship between BsmI locus and prognosis of patients with end-stage renal disease according to follow-up results were made. Results:The incidence of wild type(bb) of vitamin D receptor BsmI locus in patients with end-stage renal disease was significantly lower than that in the control group, while the incidence of mutant type(Bb and BB) was higher than that in the control group, with a dominant ratio of 1.378(P=0.004). The frequency of allele base at BsmI locus found that the incidence of A base in patients with end-stage renal disease was higher than that in control group, with an odds ratio of 1.368(P=0.01). Comparing the genotype and clinical characteristics of BsmI locus in patients with end-stage renal disease, it was found that there was no correlation between age, sex ratio, BMI, hypertension, diabetes mellitus, low density lipoprotein, high density lipoprotein, triglyceride, urea nitrogen, serum creatinine, serum calcium, phosphorus, serum albumin and serum vitamin D levels in patients with different genotypes. Indicator differences were as follows:one year after treatment, the survival rate of bb group was significantly higher than that of Bb group and BB group(P=0.003 6). K-M survival analysis showed that the median survival time was 20 months in BB group, 8 months in Bb group and 4 months in BB group(P=0.000 2). Conclusion:There is a high mutation rate of BsmI locus(GA, AA type) in patients with end-stage renal disease, that is, the mutation rate of base G to A is higher, and the survival time of patients with mutation is significantly shortened.