HMGA2 基因多态性、血清IGF-1对特发性矮小症rhGH疗效影响的交互作用分析

An Interaction Analysis of HMGA 2 Gene Polymorphism and Serum IGF-1 on rhGH Efficacy in Patients with Idiopathic Short Stature

目的探究高迁移率蛋白A2(HMGA2)基因多态性、血清胰岛素样生长因子-1(IGF-1)对特发性矮小症(ISS)重组人生长激素(rhGH)疗效影响的交互作用。方法选取2020年2月至2021年8月本院收治的ISS患儿100例,选取同期于本院接受体检的健康儿童100例纳入对照组,PCR测序分析HMGA2基因多态性情况,所有患儿均予以指导接受rhCH治疗;分析对照组和研究组HMGA2基因多态性分布和血清IGF-1表达;分析不同基因型患儿GH治疗前后IGF-1变化;分析HMGA2基因多态性联合IGF-1对ISS患儿rhGH疗效预测价值。对比不同HMGA2基因多态性ISS患儿rhGH生长情况和IGF-差异;分析不同HMGA2基因多态性和IGF-1、疗效的相关性。结果对照组和研究组儿童在HMGA2基因SNP rs1042725和SNP rs7968682分布差异显著,主要表现为在基因SNP rs1042725中,对照组TT型表达明显高于研究组,SNP rs7968682中GT型表达占比明显高于对照组(P<0.05);研究组ISS患儿血清IGF-1明显低于对照组(P<0.05);治疗后rs1042725和SNP rs7968682基因型患者的IGF-1水平较治疗前均升高,且差异具有统计学意义(均P<0.05);HMGA2基因SNP rs1042725、SNP rs7968682联合血清IGF-1评估ISS患者ROC曲线线下面积为0.935,具有较高的特异性以及灵敏度,联合检测诊断价值明显高于其他3种检测(P<0.05);经rhGH治疗后ISS患儿不同HMGA2基因多态性存在差异,SNP rs042725基因型中CT型表达ISS患儿生长情况显著优于TT和CC型(P<0.05);SNP rs7968682基因型中GT型表达ISS患儿生长情况显著优于TT和GG型(P<0.05);Spearman相关系数分析发现HMGA2基因多态性与IGF-1和疗效均呈现显著正相关(均P<0.05)。结论ISS患儿HMGA2基因多态性与正常儿童有一定差异,且ISS基因SNP rs 1042725和SNP rs7968682位点与疗效之间有显著相关性,与ISS患儿生长发育有关,可能有血清IGF-1调控有关,为临床ISS患儿的诊治提供一定基础。

Objective To investigate the interaction effect between high mobility protein A2(HMGA 2)gene polymorphism and serum insulin-like growth factor-1(IGF-1)on the efficacy of recombinant human growth hormone(rhGH)in idiopathic short stature(ISS).Methods A total of 100 children with ISS admitted to our hospital from February,2020 to August,2021 were selected for the study,while 100 healthy children who underwent physical examination in our hospital during the same period were selected as the control group.PCR sequencing was used to analyze the polymorphism of HMGA 2 gene.The distribution of HMGA 2 gene polymorphism and serum IGF-1 expression were analyzed in both control group and the study group.The changes of IGF-1 in children with different genotypes before and after GH treatment were analyzed.We analyzed the predictive value of HMGA 2 gene polymorphism combined with IGF-1 for rhGH in children with ISS.The growth of rhGH and IGF-1 in ISS children with different HMGA 2 gene polymorphisms were compared.The correlation of different HMGA 2 gene polymorphisms with IGF-1 and therapeutic effect was analyzed.Results There were significant differences in the distribution of SNPS rs1042725 and rs7968682 in HMGA 2 gene between the control group and the study group,mainly showing that the expression of TT type in the gene SNP rs1042725 was significantly higher in the control group than in the study group.The proportion of GT type expression in SNP rs7968682 was significantly higher than that in the control group(P<0.05).The serum IGF-1 in the study group was significantly lower than that in the control group(P<0.05).After treatment,IGF-1 levels in rs1042725 and SNP rs7968682 genotype patients were significantly higher than before treatment(P<0.05).The area under the ROC curve of HMGA 2 gene SNPS rs1042725 and rs7968682 combined with serum IGF-1 in evaluating ISS patients was 0.935,which had a high specificity and sensitivity.The diagnostic value of the combined detection was significantly higher than individual tests(P<0.05).There were differences in HMGA 2 gene polymorphisms in ISS children after rhGH treatment.The growth of ISS children with CT expression in SNP rs042725 genotype was significantly better than that of TT and CC genotype(P<0.05).Among SNP rs7968682 genotypes,the growth of children with ISS expressing GT genotype was significantly better than TT and GG genotype(P<0.05).Spearman correlation coefficient analysis showed that HMGA 2 gene polymorphism was significantly positively correlated with IGF-1 and efficacy(all P<0.05).Conclusion There is difference between HMGA 2 gene polymorphism in ISS children and normal children,and there is a significant correlation between SNPS rs1042725 and rs7968682 of ISS gene and therapeutic effect,which is related to the growth and development of ISS children,and may be related to the regulation of serum IGF-1.This can provide a reference basis for the diagnosis and treatment of ISS children.