维生素D受体TaqI基因多态性与儿童肾病综合征骨代谢的相关性
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摘要
目的研究维生素D受体TaqI基因多态性与儿童肾病综合征骨代谢标志物相关性,以期能否根据基因多态性预测儿童骨质疏松症风险,指导药物治疗及评估药物治疗的效果.方法研究对象为2015年5月至2016年11月收住昆明医科大学第一附属医院儿科的70例肾病综合征患儿,维生素D受体TaqI基因多态性检测方法为PCR扩增产物酶切后琼脂糖凝胶电泳检测,骨代谢标志物用生化分析.结果降钙素、25(OH)D3、甲状旁腺激素、钙、磷、碱性磷酸酶在维生素D受体TaqI基因3种基因型(TT,Tt,tt)之间的F值分别为:0.574,2.973,1.947,2.566,0.423,0.242,P值均大于0.05;镁在维生素D受体TaqI基因3种基因型(TT,Tt,tt)之间的F值9.278,P<0.001.在TT基因型患儿中,经骨化三醇治疗2周后与治疗前骨代谢标志物对比,降钙素、25(OH)D3、甲状旁腺激素、镁、磷、碱性磷酸酶t值分别为:0.796,0.290,0.295,0.574,0.830,0.933,P值均大于0.05;钙t值为4.301,P<0.001.在Tt基因型患儿中,经骨化三醇治疗2周后与治疗前骨代谢标志物对比,降钙素、25(OH)D3、甲状旁腺激素、钙、镁、磷、碱性磷酸酶t值分别为:0.722,1.298,1.391,1.511,1.671,1.045,0.368,P>0.05.在tt基因型患儿中,经骨化三醇治疗2周后与治疗前骨代谢标志物对比,降钙素、25(OH)D3、甲状旁腺激素、镁、磷、碱性磷酸酶t值分别为:1.168,1.755,1.787,2.344,1.777,1.808,P值均大于0.05;钙t值为2.458,P<0.005.结论在肾病综合征患儿中,维生素D受体TaqI多态性不能评估骨质疏松风险.TT基因型及tt基因型对骨化三醇治疗的反应性更好,经骨化三醇治疗2周后血清钙较治疗前有明显的升高,骨质疏松症的风险明显减低.
Objective In this paper,we study the relationship between vitamin D receptor TaqIgene polymorphism and bone metabolism disorder in children,snephrotic syndrome,in order to predict children's risk of osteoporosisaccording to the genetic polymorphisms,guiding drug treatment and evaluating the effect of drug treatment.Methods The object of the study was the 70 cases of children with nephrotic syndrome in pediatrics in the first affiliated hospital of Kunming Medical University from May 2015 to November 2016.Genotypes of the VDR TaqI gene polymorphism were analyzed using the PCR amplification product enzyme and agarose gel electrophoresis,bone metabolic markers with biochemical analysis.Results The F value of calcitonin(CT).25(OH) D3(VIT-D).parathyroid hormone(PTH).Calcium(Ca).phosphorus(P).alkaline phosphatase(ALP) in the three genotypes(TT TT TT) of vitamin D receptor TaqI gene polymorphism were:0.574,2.973,1.947,2.566,0.423,0.242,P>0.05.The F value of magnesium(Mg) was 9.278,P<0.001.In children with TT genotype,after calcitriol treatment2 weeks,the t value of calcitonin.25(OH) D3.parathyroidhormone.magnesium.phosphorus.alkaline phosphatase were:0.796,0.290,0.295,0.574,0.830,0.933,P >0.05 compared with treatment before.The t value of Ca was 4.301,P<0.001.In children with Tt genotype,the t value of calcitonin.25(OH) D3.parathyroid hormone.calcium.magnesium.phosphorus.alkaline phosphatase were:0.722,1.298,1.391,1.511,1.671,1.045,0.368,P>0.05.In children with tt genotype,the t value of calcitonin.25(OH) D3.parathyroid hormone.magnesium.phosphorus.alkaline phosphatase were:1.168,1.755,1.787,2.344,1.777,1.808,P>0.05;the t value of Ca was 2.458,the P<0.005.Conclusions In children with nephrotic syndrome,vitamin D receptor TaqI gene polymorphism can assess the risk of osteoporosis,tt genotype has lower risk of osteoporosis as compared with Tt genotype and TT genotype.TT genotype and tt genotype have better reactivity of calcitriol therapy.Serum calcium is significantly elevated after 2 weeks' treatment of calcitriol.The risk for osteoporosis is significantly reduced.
Objective In this paper,we study the relationship between vitamin D receptor TaqIgene polymorphism and bone metabolism disorder in children,snephrotic syndrome,in order to predict children's risk of osteoporosisaccording to the genetic polymorphisms,guiding drug treatment and evaluating the effect of drug treatment.Methods The object of the study was the 70 cases of children with nephrotic syndrome in pediatrics in the first affiliated hospital of Kunming Medical University from May 2015 to November 2016.Genotypes of the VDR TaqI gene polymorphism were analyzed using the PCR amplification product enzyme and agarose gel electrophoresis,bone metabolic markers with biochemical analysis.Results The F value of calcitonin(CT).25(OH) D3(VIT-D).parathyroid hormone(PTH).Calcium(Ca).phosphorus(P).alkaline phosphatase(ALP) in the three genotypes(TT TT TT) of vitamin D receptor TaqI gene polymorphism were:0.574,2.973,1.947,2.566,0.423,0.242,P>0.05.The F value of magnesium(Mg) was 9.278,P<0.001.In children with TT genotype,after calcitriol treatment2 weeks,the t value of calcitonin.25(OH) D3.parathyroidhormone.magnesium.phosphorus.alkaline phosphatase were:0.796,0.290,0.295,0.574,0.830,0.933,P >0.05 compared with treatment before.The t value of Ca was 4.301,P<0.001.In children with Tt genotype,the t value of calcitonin.25(OH) D3.parathyroid hormone.calcium.magnesium.phosphorus.alkaline phosphatase were:0.722,1.298,1.391,1.511,1.671,1.045,0.368,P>0.05.In children with tt genotype,the t value of calcitonin.25(OH) D3.parathyroid hormone.magnesium.phosphorus.alkaline phosphatase were:1.168,1.755,1.787,2.344,1.777,1.808,P>0.05;the t value of Ca was 2.458,the P<0.005.Conclusions In children with nephrotic syndrome,vitamin D receptor TaqI gene polymorphism can assess the risk of osteoporosis,tt genotype has lower risk of osteoporosis as compared with Tt genotype and TT genotype.TT genotype and tt genotype have better reactivity of calcitriol therapy.Serum calcium is significantly elevated after 2 weeks' treatment of calcitriol.The risk for osteoporosis is significantly reduced.
引文
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[15]MONICA GROVER,LAURA K,BACHRACH.Osteoporosis in children with chronic illnesses:diagnosis,monitoring,and treatment[J].Curr Osteoporos Rep,201,15(4):271-284.
[16]金勇,陈朝霞,血液透析联合血液灌流治疗肾性骨营养不良的疗效[J].当代医学,2015,21(25):1009-4393.
[17]范光磊,薄静莉,陈杰敏,等.慢性肾脏病患者肾性骨营养不良与骨转换生化标志物变化及相关因素分析[J].苏州大学学报(医学版),2012,32(1)0112-04.
[18]YAGUCHI A,TATEMICHI S,TAKEDA H,et al.PA21,a novel phosphate binder,improves renal osteodystrophy in rats with chronic renal failure[J].PLo S One,2017,12(7):e0180430.
[19]SHARON M,MOE,Renal osteodystrophy or kidneyinduced osteoporosis[J].Curr Osteoporos Rep,2017,15(3):194-197.
[20]杨晓,夏正坤,樊忠民,等.糖皮质激素所致儿童骨质疏松的诊断和治疗[J].医学研究生学报,2014,27(2):203-204.
[21]GHADA MOHAMED EL-MASHADA,MAHMOUD AHMED EL-HAWYA,Sally mohamed el-hefnawyb,sanaa mansour mohameda,bone mineral density in children with idiopathic nephrotic syndrome[J].J Pediatr(Rio J),2017,93(2):142-147.
[22]ACETO G,D'ADDATO O,MESSINA G,et al.Bone health in children and adolescents with steroid-sensitive nephrotic syndrome assessed by DXA and QUS[J].Pediatr Nephrol,2014,29(11):2147-2155.
[23]LEONARD M B.Glucocorticoid-induced osteoporosis in children:impact of the underlying disease[J].Pediatrics,2007,119(2):S166-174.
[24]陈晓雨,杨伟莉,杨建虹.镁与骨质疏松[J].中国骨质疏松杂志,2014,20(9):1125-1132.
[25]KAMAL A,GAMAL S M,ELGENGEHY F T,et al.Association of VDR apa I and taq I gene polymorphisms with the risk of scleroderma and behet's disease[J].Immunol Invest,2016,45(6):531-542.
[26]CHEN Y,WAN J X,JIANG D W,et la.Efficacy of calcitriol in treating glucocorticoidinduced osteoporosis in patients with nephrotic syndrome:an open-label,randomized controlled study[J].Clin Nephrol,2015,84(5):262-269.
[27]GULATI S,GODBOLE M,SINGH U,et al.Are children with idiopathic nephrotic syndrome at risk for metabolic bone disease[J].Am J Kidney Dis,2003,41(6):1163-1169.
[28]BAK M,SERDAROGLU E,GUCLU R.Prophylactic calcium and vitamin D treatments in steroid-treated children with nephrotic syndrome[J].Pediatr Nephrol,2006,21(3):350-354.
[29]ABRAMS S A,GRIFFIN I J,HAWTHORNE K M,et al.Vitamin D receptor Fok1 polymorphisms affect calcium absorption,kinetics,and bone mineralization rates during puberty[J].J Bone Miner Res,2005,20(6):945-953.
[2]LAURA K,BACHRACH M D,CATHERINE M.Bone densitometry in children and adolescents[J].Pediatrics,2014,26(5):339-346.
[3]MARK R,HANUDEL,ISIDRO B,et al.Treatment of pediatric chronic kidney disease-mineraland bone disorder[J].Curr Osteoporos Rep,2017,15(3):198-206.
[4]ONDER YAVASCAN,MD,ENGIN KOSE,MD,et al.Severe Renal Osteodystrophy in a Pediatric Patient With End-Stage Renal Disease:Sagliker Syndrome[J].Journal of Renal Nutrition the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation,2013,23(4):326-330.
[5]AKIRA ASHIDA,YUKO FUJII,Hideki Matsumura,and Hiroshi Tamai,A case of multiple vertebral compressionfractures due to glucocorticoid-inducedosteoporosis in a pediatric patient with nephrotic syndrome[J].International Journal of Clinical Pharmacology and Therapeutics,2017,55(3):264-269.
[6]SHI-YU L U,CHANG-YUAN WANG,YUE JIN,et al.The osteogenesis-promoting effects of alpha-lipoic acidagainst glucocorticoid-induced osteoporosis through the NOX4,NF-kappa B,JNK and PI3K/AKT Pathways[J].Sci Rep,2017,7(1):3331.
[7]ALESSANDRA CHESI,JONATHAN A MITCHELL,HEIDI J KALKWARF,et al.A Genomewide association study identifies two sex-specific loci,at SPTB and IZUMO3,influencing pediatric bone mineral density at multiple skeletal sites[J].J Bone Miner Res,2017,32(6):1274-1281.
[8]FRANCESCO VIERUCCI,GIUSEPPE SAGGESE,ROLANDO CIMAZ,Osteoporosis in childhood[J].Curr Opin Rheumatol,2017,29(5):535-546.
[9]SHARLA K,AMES,KENNETH J.ELLIS,et al.Vitamin D receptor gene fok1 polymorphism predicts calcium absorption and bone mineral density in children[J].J Bone Miner Res,1999,14(5):740-746.
[10]STEVEN A ABRAMS,IAN J GRIFFIN,KELI MHAWTHORNE,et al.Vitamin D receptor fok1 polymorphisms affect calcium absorption,kinetics,and bone mineralization rates during puberty[J].J Bone Miner Res,2005,20(6):945-953.
[11]XI W P,YANG J P,LI LQ,,et al.Association of vitamin D receptor gene Apa I polymorphism with vitamin D deficiency rickets[J].Zhonghua Er Ke Za Zhi,2005,43(7):514-516.
[12]FERRARI S,RIZZOLI R,SLOSMAN D,et al.Dietarycalcium and age explain the controversy surrounding the relationshipbetween bone mineral density and vitamin D receptorgene polymorphisms[J].J Bone Miner Res,1998,13(3):363-370.
[13]GUNNES M,BERG J P,HALSE J,et al.Lack of relationship between vitamin D receptor genotype and forearmbone gain in healthy children,adolescents,and young adults[J].J Clin Endocrinol Metab,1997,82(3):851-855.
[14]JONATHAN A,MITCHELL,DIANA L,et al.Genetics of pediatric bone strength[J].Bonekey Reports,2016,20(5):823.
[15]MONICA GROVER,LAURA K,BACHRACH.Osteoporosis in children with chronic illnesses:diagnosis,monitoring,and treatment[J].Curr Osteoporos Rep,201,15(4):271-284.
[16]金勇,陈朝霞,血液透析联合血液灌流治疗肾性骨营养不良的疗效[J].当代医学,2015,21(25):1009-4393.
[17]范光磊,薄静莉,陈杰敏,等.慢性肾脏病患者肾性骨营养不良与骨转换生化标志物变化及相关因素分析[J].苏州大学学报(医学版),2012,32(1)0112-04.
[18]YAGUCHI A,TATEMICHI S,TAKEDA H,et al.PA21,a novel phosphate binder,improves renal osteodystrophy in rats with chronic renal failure[J].PLo S One,2017,12(7):e0180430.
[19]SHARON M,MOE,Renal osteodystrophy or kidneyinduced osteoporosis[J].Curr Osteoporos Rep,2017,15(3):194-197.
[20]杨晓,夏正坤,樊忠民,等.糖皮质激素所致儿童骨质疏松的诊断和治疗[J].医学研究生学报,2014,27(2):203-204.
[21]GHADA MOHAMED EL-MASHADA,MAHMOUD AHMED EL-HAWYA,Sally mohamed el-hefnawyb,sanaa mansour mohameda,bone mineral density in children with idiopathic nephrotic syndrome[J].J Pediatr(Rio J),2017,93(2):142-147.
[22]ACETO G,D'ADDATO O,MESSINA G,et al.Bone health in children and adolescents with steroid-sensitive nephrotic syndrome assessed by DXA and QUS[J].Pediatr Nephrol,2014,29(11):2147-2155.
[23]LEONARD M B.Glucocorticoid-induced osteoporosis in children:impact of the underlying disease[J].Pediatrics,2007,119(2):S166-174.
[24]陈晓雨,杨伟莉,杨建虹.镁与骨质疏松[J].中国骨质疏松杂志,2014,20(9):1125-1132.
[25]KAMAL A,GAMAL S M,ELGENGEHY F T,et al.Association of VDR apa I and taq I gene polymorphisms with the risk of scleroderma and behet's disease[J].Immunol Invest,2016,45(6):531-542.
[26]CHEN Y,WAN J X,JIANG D W,et la.Efficacy of calcitriol in treating glucocorticoidinduced osteoporosis in patients with nephrotic syndrome:an open-label,randomized controlled study[J].Clin Nephrol,2015,84(5):262-269.
[27]GULATI S,GODBOLE M,SINGH U,et al.Are children with idiopathic nephrotic syndrome at risk for metabolic bone disease[J].Am J Kidney Dis,2003,41(6):1163-1169.
[28]BAK M,SERDAROGLU E,GUCLU R.Prophylactic calcium and vitamin D treatments in steroid-treated children with nephrotic syndrome[J].Pediatr Nephrol,2006,21(3):350-354.
[29]ABRAMS S A,GRIFFIN I J,HAWTHORNE K M,et al.Vitamin D receptor Fok1 polymorphisms affect calcium absorption,kinetics,and bone mineralization rates during puberty[J].J Bone Miner Res,2005,20(6):945-953.