摘要
目的探讨重组人生长激素治疗特发性矮小(ISS)患儿的临床疗效及安全性及其与维生素D受体(VDR)启动子基因多态性的相关性。方法选取90例ISS患儿为试验组,90例同期体检健康的儿童为对照组。对照组未予以任何处理;试验组予以重组人生长激素0.15 U·kg^(-1),每晚一次,皮下注射,疗程为1年。用测序仪分析2组患儿VDR启动子中CDX-2结合位点rs11568820和rs4516035的基因型分布。比较2组患儿不同基因型下的生长速率(GV)、年龄对应身高标准差积分(Ht SDSCA)、骨龄对应身高标准差积分(Ht SDSBA)、预测成年身高(PAH),以及药物不良反应的发生情况。结果 rs11568820 GG型基因:试验组治疗前和治疗后的GV分别为每年(3.12±0.32),(9.61±1.01)cm;Ht SDSCA分别为(0.29±1.32)%,(0.93±0.12)%;Ht SDSBA分别为(0.10±0.15)%,(0.86±0.02)%;PAH分别为(149.02±3.18),(159.02±3.21)cm,差异均有统计学意义(均P<0.05)。rs11568820 GA型基因:试验组治疗前和治疗后的GV分别为每年(2.92±1.21),(8.45±1.42)cm;Ht SDSCA分别为(0.42±0.15)%,(0.97±0.13)%;Ht SDSBA分别为(0.16±0.12)%,(0.83±0.13)%;PAH分别为(148.02±3.17),(156.02±3.09)cm,差异均有统计学意义(均P<0.05)。rs11568820 AA型基因:试验组治疗前和治疗后的GV分别为每年(3.27±1.21),(8.21±1.43)cm;Ht SDSCA分别为(0.37±0.14)%,(0.82±0.14)%;Ht SDSBA分别为(0.19±0.26)%,(0.79±0.14)%;PAH分别为(149.37±2.91),(158.36±2.83)cm,差异均有统计学意义(均P<0.05)。rs4516035 TT型基因:试验组治疗前和治疗后的GV分别为每年(2.71±1.63),(9.32±1.21)cm;Ht SDSCA分别为(0.35±0.21)%,(0.84±0.13)%;Ht SDSBA分别为(0.17±0.23)%,(0.76±0.13)%;PAH分别为(151.13±3.15),(158.23±2.86)cm,差异均有统计学意义(均P<0.05)。rs4516035 CT型基因:试验组治疗前和治疗后的GV分别为每年(2.46±1.32),(8.46±1.46)cm;Ht SDSCA分别为(0.32±0.24)%,(0.89±0.13)%;Ht SDSBA分别为(0.17±0.14)%,(0.72±0.13)%;PAH分别为(149.34±3.29),(157.12±3.34)cm,差异均有统计学意义(均P<0.05)。试验组发生的药物不良反应主要有血糖升高6例、膝部疼痛4例,其药物不良反应发生率为11.11%。结论 ISS与VDR启动子基因多态性无显著相关性,但与重组人生长激素治疗有明显的联系;重组人生长激素治疗ISS的临床疗效显著,且安全性较高。
Objective To observe recombinant human growth hormone idiopathic short stature (ISS) and its the clinical efficacy and safety of in the treatment of children with relationship with vitamin D receptor (VDR) promoter gene polymorphism. Methods A total of 90 cases of ISS children as the treatment group, 90 cases of healthy children as the control group. Control group was never given any treatment. Treatment group was given recombinant human growth hormone 0. 15 U·kg^-1, subcutaneously, once a night for 1 year. The genotype distribution of CDX -2 binding sites with rs11568820 and rs4516035 in the VDR promoter were analyzed by sequencer. The growth velocity (GV), height standard deviation score for age (HtSDScA), height standard deviation score for bone age ( HtSDSBA ), age peak height velocity (PAH) and adverse drug reaction were compared between two groups in diffrence genotype. Results Among the genotypes of rs3814055 GG, the main indexes in treatment group before and after treatment, GV were (3.12 ± 0.32) (9.61 ± 1.01) cm·year^-1; HtSDSCA were (0.29 ± 1.32)%, (0.93±0.12)%; HtSDSBA were (0.10 ± 0.15)%, (0.86 ± 0.02)%; PAH were (149.02 ± 3.18), ( 159.02 ± 3.21 ) cm, with significant difference ( P 〈 0.05 ). Among the genotypes of rs3814055 GA, the main indexes in treatment group before and after treatment, GV were (2. 92 ± 1.21 ), (8.45 ± 1.42)cm·year^-1 ;HtSDSCA were (0.42 ±0.15)%, (0.97 ±0.13)%; HtSDSBA were (0.16 ±0.12)%, (0.83 ±0.13)%; PAH were ( 148.02 ± 3.17 ), ( 156. 02 ± 3.09 ) cm, with significant difference ( P 〈 0. 05 ). Among the genotypes of rs11568820 AA, the main indexes in treatment group before and after treatment, GV were ( 3.27 ± 1.21 ), ( 8.21 ± 1.43 )cm.year^-1; HtSDSCA were (0.37±0.14)%, (0.82±0.14)%; HtSDSBswere (0.19±0,26), (0.79±0.14)%; PAH were ( 149.37 ± 2.91 ), ( 158.36 ±2. 83 ) cm, with significant difference ( P 〈 0. 05 ). Among the genotypes of rs4516035 TT, the main indexes in treatment group before and after treatment, GV were (2.71 ±1.63 ), (9.32±1.21)cm·year^-1; HtSDSCA were (0.35 ±0.21)%, (0.84±0.13)%; HtSDSBA were (0.17 ±0,23)%, (0.76 ± 0. 13 ) % ; PAH were ( 151.13 ± 3.15 ), ( 158.23 ± 2. 86 ) cm, with significant difference ( P 〈 0. 05 ). Among the genotypes of rs4516035 CT, the main indexes in treatment group before and after treatment, GV were (2.71±1.63) (9.32 ±1.21)cm·year^-1; HtSDSCA were ( 0. 32 ± 0. 24 ) %, ( 0. 89 ± 0. 13 ) % ; HtSDSBA were (0. 17 ±0. 14) %, (0. 72 ±0. 13) % ; PAH were ( 149.34 ± 3.29), ( 157.12 ± 3.34) cm, with significant difference (P 〈0. 05). The adverse drug reactions in treatment group were based on hyperglycemia (6 cases) and knee pain (4 cases), the incidence was 11.11%. Conclusion There is no significant correlation between ISS and VDR promoter polymorphism, but there is significant correlation with the treatment of recombinant human growth hormone. Recombinant human growth hormone has a definitive clinical efficacy and safety in the treatment of ISS.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2017年第10期884-887,共4页
The Chinese Journal of Clinical Pharmacology
基金
厦门市科技计划基金资助项目(350Z20164029)
关键词
重组人生长激素
特发性矮小
维生素D受体启动子
基因多态性
recombinant human growth hormone injection
idiopathic short stature
vitamin D receptor promoter
gene polymorphism