青春期前特发性矮小症患儿临床特征与维生素D受体BmsI基因多态性的关系

Correlation between Clinical Characteristics and Vitamin D Receptor BmsI Gene Polymorphism in Preadolescent Children with Idiopathic Short Stature

目的:探讨青春期前特发性矮小症(ISS)患儿临床特征与维生素D受体(VDR)BmsI基因多态性的关系,分析影响重组生长激素(rhGH)疗效的相关因素。方法:选取2016年3月至2018年6月我院收治的72例ISS患儿为ISS组,另选取同期参加体检的60例健康儿童为健康对照组。记录所有儿童临床资料,采用聚合酶链式反应(PCR)检测两组儿童BsmI基因多态性,采用Hardy-Weinberg遗传平衡吻合度检验法计算各基因型理论值。ISS组患儿给予rhGH治疗1年以上,并根据不同基因型分为BB、Bb及bb 3种基因型组,观察治疗3、6、12个月后不同基因型患儿生长速率和身高标准差积分(Ht-SDS)变化情况。采用Pearson分析影响rhGH疗效的相关因素。结果:治疗前,健康对照组与ISS组年龄比较差异无统计学意义(P>0.05);健康对照组儿童身高、体质量、生长速率、胰岛素样生长因子(IGF-1)和生长因子结合蛋白-3(IGFBP-3)水平明显高于ISS组(P<0.05)。健康对照组与ISS组BB、Bb及bb基因型均符合Hardy-Weinberg遗传平衡定律,两组儿童3种基因型频率及B、b等位基因频率比较差异均有统计学意义(P<0.05)。治疗前,3组基因型ISS患儿出生体质量、出生身高、身高、体质量、父亲身高、母亲身高、实际年龄、骨龄比较差异无统计学意义(P>0.05)。治疗前及治疗3个月后,BB、Bb及bb基因型组患儿生长速率和Ht-SDS比较差异无统计学意义(P>0.05);治疗6、12个月后,3组患儿生长速率和Ht-SDS均明显升高(P<0.05),且bb组患儿变化更明显(P<0.05)。相关性分析显示,初始治疗年龄与ΔHt-SDS(即Ht-SDS变化)呈负相关,初始IGF-1和IGFBP-3水平、BsmI基因多态性、初始治疗年龄、初始生长速率、治疗时间与ΔHt-SDS呈正相关。出生身高和体质量、治疗前身高和体质量、遗传靶身高、骨龄与ΔHt-SDS无明显相关性。结论:BsmI基因多态性可能与ISS发病有关,并且可能是影响rhGH疗效的因素。此外,rhGH疗效亦受IGF-1、IGFBP-3影响,越早治疗,治疗前生长速率越大,疗程越长则治疗效果越好。

Objective:To probe into the correlation between clinical characteristics and vitamin D receptor(VDR)BmsI gene polymorphism in preadolescent children with idiopathic short stature(ISS),and to analyze the influencing factors of efficacy of recombinant growth hormone(rhGH).Methods:Seventy-two children with ISS admitted into our hospital from Mar.2016 to Jun.2018 were extracted as the ISS group,and 60 healthy children participated into the physical examination during the same period were selected as the healthy control group.Clinical data of children were record.BsmI gene polymorphism of two groups was detected by polymerase chain reaction(PCR),and the theoretical value of each genotype was calculated by the Hardy-Weinberg genetic equilibrium fit test.ISS group was treated with rhGH for more than 1 year,and was divided into BB,Bb and bb genotype according to different genotypes.The growth rate and height standard deviation(Ht-SDS)of children with different genotypes were observed at 3,6 and 12 months after treatment.Pearson was used to analyze the related factors affecting the efficacy of rhGH.Results:There was no significant difference in the age between the healthy control group and the ISS group before treatment(P>0.05).The height,body weight,growth rate,insuline-like growth factor 1(IGF-1),insuline-like growth factor binding protein-3(IGFBP-3)of the healthy control group were significantly higher than those of the ISS group(P<0.05).The BB,Bb and bb genotypes of the healthy control group and ISS group were consistent with Hardy-Weinberg genetic equilibrium,and there were statistically significant differences in the frequencies of three genotypes,B and b alleles between two groups(P<0.05).Before treatment,there were no statistically significant difference in birth weight,birth height,height,body weight,height of father,height of mother,actual age and bone age among BB,Bb and bb genotypes(P>0.05).There was no significant difference in growth rate and Ht-SDS among BB,Bb and bb genotypes before treatment and after treatment of 3 months(P>0.05).After treatment of 6 and 12 months,the growth rate and Ht-SDS of three groups increased significantly(P<0.05),and the change in bb genotype was more significant(P<0.05).Correlation analysis showed that initial treatment age was negatively correlated withΔHt-SDS(changes of Ht-SDS),and initial IGF-1 and IGFBP-3 levels,BsmI gene polymorphism,initial treatment age,initial growth rate and treatment duration were positively correlated withΔHt-SDS.There was no significant correlation between birth height and body weight,height and body weight before treatment,genetic target height and bone age andΔHt-SDS.Conclusion:BsmI gene polymorphism may be related to ISS pathogenesis and may be the factor affecting the efficacy of rhGH.Meanwhile,the efficacy of rhGH is also affected by IGF-1 and IGFBP-3.The earlier the treatment,the greater the growth rate before treatment,and the longer the course of treatment,the better the treatment effect.