高迁移率蛋白A2基因多态性与青春期前特发性矮小患儿及重组人生长激素疗效的相关性研究

Relationship between high mobility group protein A2 gene polymorphisms and the efficacy of recombinant human growth hormone treatment in children with prepubertal idiopathic short stature

目的探讨河南省汉族人群中高迁移率蛋白A2(HMGA2)基因的单核苷酸多态性(SNP)与青春期前特发性矮小(ISS)患儿及重组人生长激素(rhGH)疗效之间的关系,为个体化治疗提供理论依据。方法选取2017年7月至2019年9月在郑州大学第三附属医院儿童内分泌诊疗中心诊断并经rhGH规范干预治疗至少1年的青春期前ISS患儿120例(ISS组),另选取同期体检的120例身高在正常范围的同年龄、同性别健康儿童作为对照。收集其外周血,利用分子生物学技术测定SNP位点rs1042725和rs7968682的多态性分布,分析不同基因型ISS组患儿治疗前后及对照组儿童年生长速率、身高标准差积分(HtSDS)、胰岛素样生长因子-1(IGF-1)的变化。结果1.ISS组及对照组儿童HMGA2基因rs1042725位点携带CC和CT等位基因的儿童治疗前生长速率均高于TT等位基因组[(4.33±0.64)cm/年,(3.95±0.45)cm/年;(6.35±0.41)cm/年,(6.12±0.32)cm/年比(3.76±0.52)cm/年,(5.96±0.42)cm/年],差异均具有统计学意义(均P<0.05)。2.ISS患儿HMGA2基因rs7968682位点GT基因型治疗后年龄及骨龄HtSDS增长值均高于TT基因型[(0.74±0.30)cm/年比(0.63±0.24)cm/年,(0.16±0.05)cm/年比(0.14±0.05)cm/年],差异均具有统计学意义(均P<0.05)。结论河南省汉族人群HMGA2基因SNP位点(rs1042725)的多态性与ISS的程度可能具有相关性,而SNP位点(rs7968682)的多态性与rhGH的疗效可能有关。

Objective To investigate the relationship of single nucleotide polymorphism(SNP)of high mobi-lity group protein A2(HMGA2)gene with prepubertal idiopathic short stature(ISS)and the efficacy of recombinant human growth hormone(rhGH)in Han population of Henan Province.Methods A total of 120 children who were diagnosed with prepubertal ISS and treated with rhGH standards for at least one year from July 2017 to September 2019 at the Children′s Endocrinology Clinic of the Third Affiliated Hospital of Zhengzhou University were enrolled in the ISS group of this study.Meanwhile,120 healthy children(control group)of the same age and gender whose height was within the normal range were selected as controls.Their peripheral blood was collected,and the polymorphism distributions of SNP loci(rs1042725 and rs7968682)were determined by molecular biology.Analysis was carried out to specify the annual growth rate,height standard deviation score(HtSDS),and insulin-like growth factor-1(IGF-1)of ISS children with different genotypes(before and after treatment)and those in the control group.Results(1)In both ISS group and control group,children with CC and CT alleles at rs1042725 locus of HMGA2 had higher growth rate than those with TT allele before treatment[(4.33±0.64)cm/year,(3.95±0.45)cm/year;(6.35±0.41)cm/year,(6.12±0.32)cm/year vs.(3.76±0.52)cm/year,(5.96±0.42)cm/year],therefore the difference were statistically significant(all P<0.05).(2)After treatment with GT genotype at the HMGA2 rs7968682 locus in children with ISS,the growth rate of age and bone HtSDS was higher than that of TT genotype[(0.74±0.30)cm/year vs.(0.63±0.24)cm/year,(0.16±0.05)cm/year vs.(0.14±0.05)cm/year],therefore the differences were statistically significant(all P<0.05).Conclusions The polymorphism of the HMGA2 SNP locus(rs1042725)in the Han population of Henan province may be related to ISS level,while the polymorphism of the SNP locus(rs7968682)may be related to rhGH efficacy.