Turner综合征患儿临床特征、生长激素受体基因Ex3多态性以及与rhGH疗效相关性分析

目的探讨Turner综合征(TS)患儿生长激素受体(GHR)基因Ex3多态性以及影响重组生长激素(rhGH)治疗疗效的相关因素。方法选取2016年3月-2017年6月来我院内分泌专科就诊明确诊断为TS患儿36例作为研究对象,并选取同期参加体检的健康儿童60例作为对照。记录所有儿童临床资料,PCR检测2组儿童 GHR Ex3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的理论值。TS儿童给予rhGH治疗1年以上并根据基因型分为3组,治疗后第3、6、12个月观察不同基因型儿童生长速率和身高标准差积分(Ht-SDS)的变化;Person分析影响rhGH治疗的因素。结果治疗前健康组与TS组儿童年龄相比较差异无统计学意义(P>0.05);健康组儿童身高、体重、生长速率、IGF-1及IGFBP-3明显高于TS组(P<0.05)。健康组与TS组fl/f1GHR、fl/d3-GHR及d3/d3-GHR基因型均符合Hardy-Weinberg遗传平衡定律,2组儿童间3种基因型频率差异以及f1、d3等位基因频率差异均存在统计学意义(P<0.05)。治疗前,3组基因型TS患儿出生体重、出生身高、身高、体重、父亲身高、母亲身高、实际年龄、骨龄相比较差异无统计学意义(P>0.05)。治疗前及治疗3个月后,3组中患儿生长速率和Ht-SDS差异无统计学意义(P>0.05);治疗6个月和治疗12个月后,3组患儿生长速率和Ht-SDS均明显升高(P<0.05),且d3/d3GHR组患儿变化更为明显(P<0.05)。相关性分析显示,初始治疗年龄与△Ht-SDS明显负相关,初始IGF-1和IGFBP6水平、GHR Ex3基因多态性、初始治疗年龄、初始生长速率、治疗时间与△Ht-SDS明显正相关;出生身长和体重、治疗前身高和体重、遗传靶身高、骨龄与△Ht-SDS无明显相关性。结论 GHR Ex3基因多态性与TS发病有关,也是影响rhGH治疗的因素。rhGH疗效还受IGF-1、IGFBP6影响,且越早治疗、治疗前生长速率越大、疗程越长治疗效果越好。

Clinical characteristics of children with Turner syndrome,growth hormone receptor gene Ex3 polymorphism and correlation with rh GH efficacy

Objective:To investigate the growth hormone receptor(GHR)gene Ex3 polymorphism in children with Turner syndrome(TS)and related factors affecting the therapeutic effect of recombinant growth hormone(rhGH).Methods:From March 2016 to June 2017,a total of 36 patients with TS diagnosed in the endocrinology department of our hospital were selected as the study subjects,and 60 healthy children who participated in the physical examination at the same time were selected as controls.All clinical dates of children were record.The GHR Ex3 gene polymorphism was detected by PCR in two groups.The theoretical value of each genotype was calculated by Hardy-Weinberg genetic equilibrium test.TS children were given rhGH for more than 1 year and were divided into 3 groups according to genotype.TS children were given rhGH for more than 1 year and were divided into 3 groups according to genotype.The growth rate and height standard deviation(Ht-SDS)of children with different genotypes were observed at 3,6,and 12 months after treatment.Factors of affecting rhGH treatment were analyzed by Person.Results:There was no significant difference in the age between the healthy group and the TS group before treatment(P>0.05).The height,weight,growth rate,IGF-1 and IGFBP-3 of the healthy group were significantly higher than those of the TS group(P<0.05).The fl/f1GHR,fl/d3-GHR and d3/d3-GHR genotypes in the healthy and TS groups were consistent with the Hardy-Weinberg genetic equilibrium law.The differences in the frequency of the three genotypes and the frequency of the f1 and d3 alleles between the two groups were observed.All were statistically significant(P<0.05).Before treatment,there were no significant differences in birth weight,birth height,height,weight,father height,mother height,actual age and bone age among the three groups of genotype TS children(P>0.05).There was no significant difference in growth rate and Ht-SDS between the three groups before treatment and after 3 months of treatment(P>0.05).After 6 months and 12 months of treatment,the growth rate and Ht-SDS of the three groups were significant.The increase was higher(P<0.05),and the change in the d3/d3GHR group was more significant(P<0.05).Correlation analysis showed that the initial treatment age was significantly negatively correlated with △Ht-SDS,and the initial IGF-1 and IGFBP6 levels,GHR Ex3 gene polymorphism,initial treatment age,initial growth rate,and treatment time were positively correlated with △Ht-SDS;birth length and There was no significant correlation between body weight,pre-treatment height and weight,genetic target height and bone age,and △Ht-SDS.Conclusion:The GHR Ex3 gene polymorphism is associated with the pathogenesis of TS and is also a factor influencing the treatment of rhGH.The curative effect of rhGH is also affected by IGF-1 and IGFBP6,and the earlier the treatment,the greater the growth rate before treatment,and the longer the treatment,the better the treatment effect.