VDR基因多态性与维持性血液透析患者肾性骨营养不良的关系
|
摘要
目的通过研究维持性血液透析(MHD)患者维生素D受体(VDR)基因多态性的变化,了解VDR基因多态性与肾性骨营养不良之间的关系。方法选择2016年1月至2017年11月武汉市第五医院就诊的MHD患者200例,年龄40～65岁,采用双能X线吸收测量法(DEXA)测量VDR BB基因型、VDR Bb基因型、VDR bb基因型3种不同基因型的骨密度水平。应用DEXA对股骨颈骨密度进行测量,并调查患者的一般情况,采用Pearson检验进行相关性分析,了解VDR基因多态性与骨代谢指标之间的相关性。结果 VDR bb基因型骨密度Z-Score值低于VDR Bb基因型,VDR Bb基因型的骨密度Z-Score值低于VDR BB基因型,不同基因型的MHD患者骨密度Z-Score值之间的差异具有统计学意义(P <0.05); MHD患者低骨量的发生率和骨矿质缺乏的发生率分别约为30.0%和20.0%,VDR不同基因型的MHD患者低骨量及骨矿质缺乏的患病率差异具有统计学意义(P <0.05);VDR bb患者骨代谢指标(钙、磷、ALP、PTH)与VDR BB、VDR Bb比较,差异均有统计学意义(P <0.05); MHD患者的骨密度与体质量相关(r=-0.260,P <0.05),与年龄和身高无相关性。结论 MHD患者肾性骨营养不良受遗传因素的影响,VDR基因BsmI多态性影响骨代谢,VDR基因多态性可以作为肾性骨营养不良的预测因子,并对临床治疗提供参考依据。
Objective To investigate the relationship between VDR gene polymorphism and bone mineral density( BMD) in patients undergoing maintenance hemodialysis by analyzing the changes in vitamin D receptor( VDR) gene polymorphism. Methods Two hundred patients undergoing maintenance hemodialysis from January 2016 to November 2017 were selected,aged 20-65 years. The BMD of three different genotypes,VDR BB genotype,VDR Bb genotype and VDR bb genotype were measured.The femoral neck BMD was measured with DEXA and the general condition of the patients was investigated. Pearson test was used to analyze the correlation between VDR gene polymorphism and bone metabolism index. Results The Z-score of BMD in VDR bb genotype was lower than that in VDR Bb genotype,while that in VDR Bb genotype was lower than that in VDR BB genotype. Amongst the Z-score values of BMD in maintenance hemodialysis patients with different genotypes,the difference was statistically significant( P < 0.05). The incidence of low bone mass and bone mineral deficiency in patients with maintenance hemodialysis was 30.0% and 20.0%,respectively. For different VDR genotypes,the prevalence of low bone mass and bone mineral deficiency in patients with maintenance hemodialysis wassignificantly different( P < 0.05). There was significant difference in the bone metabolic parameters( calcium,phosphorus,ALP and PTH) between VDR BB and VDR Bb( P < 0.05). The BMD of maintenance hemodialysis patients was related to body weight( r =-0.260,P < 0.05),but not with age or height. Conclusions Renal bone dystrophy in patients with chronic maintenance hemodialysis is affected by genetic factors. BsmI polymorphism of VDR gene affects bone metabolism.VDR gene polymorphism can be used as a predictor of renal bone dystrophy and provide reference for clinical treatment.
Objective To investigate the relationship between VDR gene polymorphism and bone mineral density( BMD) in patients undergoing maintenance hemodialysis by analyzing the changes in vitamin D receptor( VDR) gene polymorphism. Methods Two hundred patients undergoing maintenance hemodialysis from January 2016 to November 2017 were selected,aged 20-65 years. The BMD of three different genotypes,VDR BB genotype,VDR Bb genotype and VDR bb genotype were measured.The femoral neck BMD was measured with DEXA and the general condition of the patients was investigated. Pearson test was used to analyze the correlation between VDR gene polymorphism and bone metabolism index. Results The Z-score of BMD in VDR bb genotype was lower than that in VDR Bb genotype,while that in VDR Bb genotype was lower than that in VDR BB genotype. Amongst the Z-score values of BMD in maintenance hemodialysis patients with different genotypes,the difference was statistically significant( P < 0.05). The incidence of low bone mass and bone mineral deficiency in patients with maintenance hemodialysis was 30.0% and 20.0%,respectively. For different VDR genotypes,the prevalence of low bone mass and bone mineral deficiency in patients with maintenance hemodialysis wassignificantly different( P < 0.05). There was significant difference in the bone metabolic parameters( calcium,phosphorus,ALP and PTH) between VDR BB and VDR Bb( P < 0.05). The BMD of maintenance hemodialysis patients was related to body weight( r =-0.260,P < 0.05),but not with age or height. Conclusions Renal bone dystrophy in patients with chronic maintenance hemodialysis is affected by genetic factors. BsmI polymorphism of VDR gene affects bone metabolism.VDR gene polymorphism can be used as a predictor of renal bone dystrophy and provide reference for clinical treatment.
引文
[1]Bover J,Lloret MJ,DaS ilva I,et al. Role of vitamin D receptor activators in peritoneal dialysis[J]. Contributions to nephrology,2012,178(5):124-142.
[2]Sueta S,Morozumi K,Takeda A,et al. Ability of vitamin D receptor activator to prevent pulmonary congestion in advanced chronic kidney disease[J]. Clinical and experimental nephrology,2015,19(3):371-378.
[3]安书强,杨倩,贾晓娟,等.慢性肾功能衰竭血液灌流串联血液透析滤过清除瘦素、甲状旁腺素效果研究[J].武警医学,2011,22(4):284-286.
[4]Avila M,Prado C,Ventura MD,et al. Vitamin D receptor gene,biochemical bone markers and bone mineral density in Mexican women on dialysis[J]. European Renal Association,2010,25(7):2259-2265.
[5]Christakos S,Dhawan P,Verstuyf A,et al. Vitamin D:Metabolism,molecular mechanism of action,and pleiotropic effects[J].Physiol Rev,2016,96(1):365-408.
[6]Jawadi AH,Wakeel A,Tamimi W,et al. Association analysis between four vitamin D receptor gene polymorphisms and developmental dysplasia of the hip[J]. J Genet,2018,97(4):925-930.
[7]Cortadellas O,Fernández del Palacio MJ,Talavera J,et al. Calcium and phosphorus homeostasis in dogs with spontaneous chronic kidney disease at different stages of severity[J]. JVet Intern Med,2010,24(1):73-79.
[8]Yamada S,Tsuruya K,Yoshida H,et al. Factors Associated with the Serum Myostatin Level in Patients Undergoing Peritoneal Dialysis:Potential Effects of Skeletal Muscle Mass and Vitamin D Receptor Activator Use[J]. Calcified tissue international,2016,99(1):13-22.
[9]贾艳丽,刘惠兰.甲状旁腺素及骨转运指标的测定在维持性血液透析患者肾性骨病诊断中的意义[J].首都医科大学学报,2010,31(6):803-807.
[10]中国健康促进基金会骨质疏松防治中国白皮书编委会.骨质疏松症中国白皮书[J].中华健康管理学杂志,2009,6(3):148-153.
[11]Suri P,Morgenroth DC,Hunter DJ,et al. Epidemiology of Osteo-arthritis and Associated Comorbidities[J]. PMR,2012,4(5):S10-S19.
[12]陈为坚,叶伟,苏培强,等.汉族人维生素D受体基因TruⅠ和FokⅠ多态性与腰椎间盘退变的关系[J].中国矫形外科杂志,2007,15(5):373-375+379.
[13]Santos Castaneda,Jorge A. Roman-Blas,et al. Subchondral bone as a key target for osteoarthritis treatment[J]. Biochemical Pharmacology,2012,83(3):315-323.
[14]Ramonda R,Lorenzin M,Modesti V,et al. Serological markers of erosive hand osteoarthritis[J]. Eur J Intern Med,2013,24(1):11-15.
[15]Wysoczańska-Klaczyńska A,S'lzak A,Hetman M,et al. The impact of VDR gene polymorphisms on obesity,metabolic changes,bone mass disorders and neoplastic processes[J]. Pediatr Endocrinol Diabetes Metab,2018,24(2):96-105.
[16]赵云艽,邱国萍.血液灌流联合血液透析治疗继发性甲状旁腺功能亢进的疗效观察[J].中国当代医药,2012,19(3):38-39.
[17]Ishimura E,Okuno S,Ichii M,et al. Relationship between serum sclerostin,bone metabolism markers,and bone mineral density in maintenance hemodialysis patients[J]. J Clin Endocrinol Metab,2014,99(11):4315-4320.
[18]Hodkova M,Dusilova-Sulkova S,Kalousova M,et al. Influence of oral vitamin E therapy on micro-inflammation and cardiovascular disease markers in chronic hemodialysis patients[J]. Ren Fail,2016,28(5):395-399.
[19]Dabirnia R,Mahmazi S,Taromchi A,et al. The relationship between vitamin D receptor(VDR)polymorphism and the occurrence of osteoporosis in menopausal Iranian women[J]. Clin Cases Miner Bone Metab,2016,13(3):190-194.
[20]Chang B,Schlussel Y,Sukumar D,et al. Influence of vitamin D and estrogen receptor gene polymorphisms on calcium absorption:BsmI predicts a greater decrease during energy restriction[J].Bone,2015,81(12):138-144.
[2]Sueta S,Morozumi K,Takeda A,et al. Ability of vitamin D receptor activator to prevent pulmonary congestion in advanced chronic kidney disease[J]. Clinical and experimental nephrology,2015,19(3):371-378.
[3]安书强,杨倩,贾晓娟,等.慢性肾功能衰竭血液灌流串联血液透析滤过清除瘦素、甲状旁腺素效果研究[J].武警医学,2011,22(4):284-286.
[4]Avila M,Prado C,Ventura MD,et al. Vitamin D receptor gene,biochemical bone markers and bone mineral density in Mexican women on dialysis[J]. European Renal Association,2010,25(7):2259-2265.
[5]Christakos S,Dhawan P,Verstuyf A,et al. Vitamin D:Metabolism,molecular mechanism of action,and pleiotropic effects[J].Physiol Rev,2016,96(1):365-408.
[6]Jawadi AH,Wakeel A,Tamimi W,et al. Association analysis between four vitamin D receptor gene polymorphisms and developmental dysplasia of the hip[J]. J Genet,2018,97(4):925-930.
[7]Cortadellas O,Fernández del Palacio MJ,Talavera J,et al. Calcium and phosphorus homeostasis in dogs with spontaneous chronic kidney disease at different stages of severity[J]. JVet Intern Med,2010,24(1):73-79.
[8]Yamada S,Tsuruya K,Yoshida H,et al. Factors Associated with the Serum Myostatin Level in Patients Undergoing Peritoneal Dialysis:Potential Effects of Skeletal Muscle Mass and Vitamin D Receptor Activator Use[J]. Calcified tissue international,2016,99(1):13-22.
[9]贾艳丽,刘惠兰.甲状旁腺素及骨转运指标的测定在维持性血液透析患者肾性骨病诊断中的意义[J].首都医科大学学报,2010,31(6):803-807.
[10]中国健康促进基金会骨质疏松防治中国白皮书编委会.骨质疏松症中国白皮书[J].中华健康管理学杂志,2009,6(3):148-153.
[11]Suri P,Morgenroth DC,Hunter DJ,et al. Epidemiology of Osteo-arthritis and Associated Comorbidities[J]. PMR,2012,4(5):S10-S19.
[12]陈为坚,叶伟,苏培强,等.汉族人维生素D受体基因TruⅠ和FokⅠ多态性与腰椎间盘退变的关系[J].中国矫形外科杂志,2007,15(5):373-375+379.
[13]Santos Castaneda,Jorge A. Roman-Blas,et al. Subchondral bone as a key target for osteoarthritis treatment[J]. Biochemical Pharmacology,2012,83(3):315-323.
[14]Ramonda R,Lorenzin M,Modesti V,et al. Serological markers of erosive hand osteoarthritis[J]. Eur J Intern Med,2013,24(1):11-15.
[15]Wysoczańska-Klaczyńska A,S'lzak A,Hetman M,et al. The impact of VDR gene polymorphisms on obesity,metabolic changes,bone mass disorders and neoplastic processes[J]. Pediatr Endocrinol Diabetes Metab,2018,24(2):96-105.
[16]赵云艽,邱国萍.血液灌流联合血液透析治疗继发性甲状旁腺功能亢进的疗效观察[J].中国当代医药,2012,19(3):38-39.
[17]Ishimura E,Okuno S,Ichii M,et al. Relationship between serum sclerostin,bone metabolism markers,and bone mineral density in maintenance hemodialysis patients[J]. J Clin Endocrinol Metab,2014,99(11):4315-4320.
[18]Hodkova M,Dusilova-Sulkova S,Kalousova M,et al. Influence of oral vitamin E therapy on micro-inflammation and cardiovascular disease markers in chronic hemodialysis patients[J]. Ren Fail,2016,28(5):395-399.
[19]Dabirnia R,Mahmazi S,Taromchi A,et al. The relationship between vitamin D receptor(VDR)polymorphism and the occurrence of osteoporosis in menopausal Iranian women[J]. Clin Cases Miner Bone Metab,2016,13(3):190-194.
[20]Chang B,Schlussel Y,Sukumar D,et al. Influence of vitamin D and estrogen receptor gene polymorphisms on calcium absorption:BsmI predicts a greater decrease during energy restriction[J].Bone,2015,81(12):138-144.