青少年特发性脊柱侧凸RANK基因多态性及侧凸进展预测因素研究

发布时间：2018-04-17 20:03

本文选题：青少年特发性脊柱侧凸 + 核因子κB受体活化子　；参考：《南京大学》2015年博士论文

【摘要】：目的：探讨核因子κB受体活化子(receptor activator of nuclear factor-κB,RANK)基因多态性与青少年特发性脊柱侧凸(adolescent idiopathic scoliosis, AIS)易感性之间的相关性。方法：本研究实验组为2009年2月至2013年7月于我院行支具或手术治疗的主弯Cobb角大于20°的女性AIS患儿共450例,平均年龄14.8±2.9岁(10-18岁)。对照组为例行健康体检的我院周围地区无血缘关系的健康青少年女性400名,平均年龄15.1±2.3岁(10-17岁)。所有AIS患儿均有身高、体重及BMI(Body Mass Index)等资料。rs1805034和rs35211496作为RAN K的tagSNP被选中并采用Taqman-MGB技术进行分型,此2个tagSNP可以覆盖整个RANK基因。采用Hardy-Weinberg遗传平衡定律对等位基因的频率进行检验,以了解各基因频率是否符合遗传平衡和有群体代表性。采用R×C表χ2检验比较实验组和对照组SNP位点基因型及等位基因频率分布的差异。另外,采用单因素方差分析比较实验组内不同基因型患儿主弯Cobb角及BMI间的差异。结果：rs1805034和rs35211496的基因型在实验组和对照组中的分布均符合Hardy-Weinberg遗传平衡定律。rs1805034和rs35211496的基因型及等位基因频率两组间无显著统计学差异(P0.05)。单因素方差分析示rs1805034和rs35211496基因型及等位基因频率与AIS患儿主弯Cobb角及BMI无显著相关性(P0.05)。结论：RANK基因不是AIS的易感基因,其与AIS患儿的主弯Cobb角及BMI亦无显著相关性。目的：比较脊柱生长速率(spinal growth velocity, SGV)和身高生长速率(height velocity, HV)与青少年特发性脊柱侧凸(adolescent idiopathic scoliosis, AIS)患儿侧凸进展速率(angle velocity, AV)之间的相关性,探讨SGV对AIS侧凸进展的预测价值。方法：本研究回顾性分析于我院行正规支具治疗的、右胸弯型、最终侧凸进展大于5°的未成熟AIS女孩。记录患儿每次随访时的实足年龄、身高、主弯Cobb角、脊柱长度和Risser征等参数,并计算每次随访时的HV、AV和SGV。最终确定每例患儿的身高生长高峰(peak height velocity, PHV)和脊柱生长高峰(peak spine growth velocity, PSGV)。相关性分析采用Spearman相关系数,多元线性回归分析AV的影响因素,逻辑回归分析AV大于5°/年的高危因素。结果：共26例女性AIS患儿入选本研究,初诊时平均Cobb角为24.1±3.3°,末次随访时平均Cobb角为35.8±7.9°。随访中平均AV为6.3±8.9°/年,平均PHV和PSGV分别为9.8±3.5 cm/年和40.9±19.2 mm/年。多元线性回归示AV与SGV(B=0.226,P=0.001)呈显著线性相关,而与HV(B=0.173,P=0.268)无显著相关性。逻辑回归示PSGV (OR=4.479, P=0.001)是AV大于5°/年的高危因素,而PHV(OR=2.013,P=0.102)并未进入预测模型。结论：脊柱生长速率比身高生长速率能更准确的预测AIS患儿侧凸进展速率,较高的脊柱生长速率预示侧凸进展的高风险。目的：比较侧凸Cobb角初始矫正速率(angle reduction velocity, ARV)和初始矫正率(correction rate, CR)对青少年特发性脊柱侧凸(adolescent idiopathic scoliosis,AIS)患儿侧凸进展的预测价值,并提出ARV对AIS侧凸进展的理想预测值。方法：本研究回顾性分析于我院门诊符合SRS标准并行正规支具治疗的AIS女孩,患儿每次随访间隔为3-6个月,直至因发育成熟或侧凸进展而停止支具治疗。记录患儿每次随访时的人口统计学资料、成熟度指标和侧凸Cobb角等,并计算每例患儿的ARV和CR。根据患儿最终侧凸Cobb角的变化情况分为两组：进展组Cobb角进展≥6°,非进展组Cobb角进展6°。两组之间的比较用独立样本t检验,并应用逻辑回归分析比较ARV和CR对AIS患儿侧凸进展的预测能力。结果：本研究共入选95例AIS患儿,其中非进展组76例,进展组19例。独立样本t检验示非进展组和进展组的ARV(12.8±21.4°/年 VS -5.4±15.2°/年,P=0.001)和CR(12.1%±20.7% VS-5.8%±18.0%,P=0.001)有显著统计学差异。逻辑回归示初诊时的实足年龄(OR=1.742,P=0.043)和ARV (OR=1.057,P=0.002)可以用于预测AIS患儿侧凸进展风险。ARV对AIS侧凸进展与否的理想预测值为10°/年(OR=8.959,P=0.005)。结论：行支具治疗的AIS患儿中,初始矫正速率比初始矫正率具有更高的侧凸进展预测能力。初行支具治疗后第一次随访时,初始矫正速率低于100／年预示患儿具有较高的侧凸进展风险。目的：探讨尺桡骨远端(distal radius and ulna, DR U)骨龄评分系统与其他成熟度指标之间的相关性,并评估DRU系统在行支具治疗的青少年特发性脊柱侧凸(adolescent idiopathic scoliosis, AIS)患儿侧凸进展中的预测价值。方法：本长期纵向随访研究选取40例右胸弯型的女性AIS患儿,所有患儿均行标准化的支具治疗,随访间隔为3-6个月直到停支具。每次随访时记录并测量患儿如下参数：实足年龄、身高、主弯Cobb角、脊柱长度、Risser征、DSA(digital skeletal age)评分和DRU评分。据此计算患儿每次随访时的身高生长速率(heightvelocity, HV)、Cobb角进展速率(angle velocity, AV)和脊柱生长速率(spine growth velocity, SGV)。比较分析DRU评分与各成熟度指标的相关性以评估其对AIS患儿侧凸进展的预测价值。结果：40例患儿初诊时的平均年龄为11.1±1.5岁,桡骨评分平均为R6.5±1.1,尺骨评分平均为U4.5±1.2。相关性分析示桡骨和尺骨评分之间具有良好的线性相关(r=0.723,P0.001)。桡骨评分介于R7-R9之间和尺骨评分介于U5-U7之间与DSA评分400-500之间、高HV、高SGV和高AV均呈显著相关(P0.05)。结论：桡骨评分介于R7-R9之间和尺骨评分介于U5-U7之间与高HV、高SGV和高AV呈显著相关。DRU评分是一种良好的评估AIS患儿生长潜能及侧凸进展风险的指标,值得临床推广使用。目的：利用SRS(scoliosis research society)标准分析发育成熟的青少年特发性脊柱侧凸(adolescent idiopathic scoliosis,AIS)患儿在停止支具治疗后的长期随访中的侧凸进展情况,并探讨其相关因素。方法：回顾性分析于我院门诊符合SRS支具治疗标准的女性AIS患儿200例,平均初诊年龄12.08±1.2岁。所有患儿均随访至支具治疗结束后至少2年,且至少具有初次佩戴支具、停支具0个月、停支具后6个月、停支具后1年、停支具后2年及末次随访时的资料。于每次随访时的全脊柱正位片上测量主弯侧凸Cobb角,并应用SRS标准评估侧凸进展超过5°的患儿比例、因侧凸进展而行手术治疗的患儿比例、侧凸Cobb角大于45°的患儿比例及侧凸进展度数和进展速率。侧凸进展分别定义为停支具后2年时侧凸进展超过5°和停支具后2年时侧凸Cobb角超过450,比较分析应用独立样本t检验。结果：与初停支具时相比,停止支具后6个月、1年、2年及末次随访时的侧凸进展超过5°的患儿比例分别为25.0%、30.0%、46.5%和43.5%；因侧凸进展而行手术治疗的患儿比例分别为0%、0%、1%和1%；侧凸Cobb角大于45°的患儿比例分别为2.7%、5.5%、8.2%和12.0%；侧凸进展度数分别为2.6±5.8°、3.5±5.8°、5.1±6.5°和5.4±7.4°；侧凸进展速率分别为0.34±0.83°/月、0.16±±0.56°/月、0.13±0.39°/月和0.006±0.28°/月。独立样本t检验示,停止支具治疗后的AIS患儿中,非进展组和进展组停支具时的Cobb角(P0.05)有显著统计学差异。结论：行支具治疗的AIS患儿从初次停支具至停支具后至少2年随访中侧凸最终进展大于5°的比例为43.5%,而侧凸进展风险最高期为停止支具后的6个月内。停支具时的侧凸Cobb角越大则发生侧凸进展的风险越高。
[Abstract]:Objective : To investigate the correlation between the polymorphism of nuclear factor - 魏B and the susceptibility of adolescent idiopathic scoliosis ( AIS ) . The results showed that the genotypes of rs1805034 and rs35211496 had no significant correlation between the genotype and BMI of children with AIS . PHV ) and peak spine growth velocity ( PSGV ) . Objective : To study the predictive value of scoliosis in children with idiopathic scoliosis ( AIS ) . Results : The incidence of scoliosis in children with AIS was significantly higher than that in patients with AIS . Results : The results showed that the incidence of scoliosis in patients with AIS was higher than 5 掳 / year , while PHV ( OR = 2.013 , P = 0 . 102 ) was significantly higher than that of HV ( B = 0 . 173 , P = 0 . 102 ) . P = 0.001 ) and CR ( 12.1 % 卤 20.7 % VS - 5.8 % 卤 18.0 % , P = 0.001 ) . Conclusion : In patients with AIS , the initial correction rate is higher than the initial correction rate . In the first follow - up period , 40 patients with right thoracic curve were treated with standardized brace . The results were as follows : The height growth rate ( HV ) , the angle velocity ( AV ) and the spine growth velocity ( SGV ) of the children with idiopathic scoliosis ( AIS ) were recorded and measured at each follow - up . The results showed that the height growth rate ( HV ) , the angle velocity ( AV ) and the spine growth velocity ( SGV ) of the children were measured at each follow - up . The correlation analysis showed that the mean age was 11.1 卤 1.5 years , the mean radius score was 6.5 卤 1.1 , the average radius was 6.5 卤 1.2 . The correlation analysis showed that there was a good linear correlation between radius and ulnar score ( r = 0.723 , P0.001 ) . The results showed that the index of radial bone was between R7 and R9 and between U5 - U7 and DSA score of 400 - 500 , high HV , high SGV and high AV were significantly correlated ( P0.05 ) .
The proportion of children undergoing surgery was 0 % , 0 % , 1 % and 1 % , respectively .
The proportions of the children with scoliosis more than 45 掳 were 2.7 % , 5.5 % , 8.2 % and 12.0 % , respectively .
The progress degrees of scoliosis were 2.6 卤 5.8 掳 , 3.5 卤 5.8 掳 , 5.1 卤 6.5 掳 and 5.4 卤 7.4 掳 , respectively ;
Conclusion : The incidence of scoliosis progression at least 2 years follow - up from the first stop to the rest of the patients with AIS is 43 . 5 % , while the maximum risk of scoliosis is at least 6 months after stopping the brace .

【学位授予单位】：南京大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R682.3

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