| BackgroundIdiopathic short stature(ISS)is a type of dwarfism without any clear etiology at present,accounting for 60%-80%of the children born with short stature[1-3].Recombinant human growth hormone(rhGH)is the treatment of choice for children with ISS.However,considering its high price and inconsistent therapeutic effects,improving the sensitivity of rhGH therapy has become the current research hotspo[4].Previous studies have suggested that the growth hormone-insulin like growth factor-1(GH-IGF-1)axis is an important signaling pathway in promoting linear growth and is closely linked with ISS.Recent studies have found that the factors regulating the cell cycle are also related to ISS[5].The high mobility group protein A2(HMGA2)gene encodes a small molecule protein with high mobility in gel electrophoresis,which is closely associated with the regulation of the cell cycle,and lack of which can cause porcine dwarfism[6].It has also been reported that the HMGA2-PLAG1-IGF2 pathway disorder is connected to small for gestational age(SGA)newborns[7].In addition,among the 19 single nucleotide polymorphism(SNP)sites of the HMGA2 gene,the SNPrs1042725 site is significantly correlated with the Han population's height in China[8].Domestic studies have demonstrated that the SNPrs7968682 locus of the HMGA2 gene is related to adult male height[9].Furthermore,height-related genetic polymorphisms could have an impact on the eficacy of rhGH therapy[10].However,there is no correlation study carried on HMGA2 gene polymorphism and rhGH therapy efficacy in prepubertal ISS children both domestically and abroad.Consequently,in this study,SNPrs1042725 and SNPrs7968682 sites in the HMGA2 gene,which are closely associated with height,were selected to explore the relationship between HMGA2 gene polymorphism and rhGH individualized treatment in ISS children by comparing the clinical indicators following rhGH therapy with different genotypes at the two sites.ObjectiveTo provide a theoretical basis for the clinical individualized treatment of ISS.This study discusses the relationship among single nucleotide polymorphisms(SNP)of high mobility group protein gene A2(HMGA2)children with prepubetal idiopathic short stature(ISS)and the efficacy of recombinant human growth hormone(rhGH).Methods120 children selected for an ISS group were diagnosed with prepubertal idiopathic short stature from July 2017 to September 2019 at the Children's Endocrinology Clinic of the Third Affiliated Hospital of Zhengzhou University and they have been treated with rhGH standards for at least one year.Meanwhile 120 healthy children whose height was ± 1 standard deviation(SD)within the normal range of the same age and gender who came to our hospital for physical examination during the same period were collected as the control group.The peripheral blood of 2ml was collected in the morning,the whole genome DNA was extracted and the target genes were amplified by polymerase chain reaction(PCR).The polymorphism distribution of SNP locus rs1042725 and rs7968682 were sequenced by sequencing instrument to compare the gene distribution frequency and analyze the changes of the bone age(BA),growth velocity(GV),height standard deviation score(HtSDS),insulin-like growth factor(IGF-1),liver and kidney function,thyroid function,blood glucose and other clinical indicators of the children with different genotypes in ISS group before and after treatment and those in the control group.The experimental data were analyzed by SPSS21.0 software,The count data were expressed in terms of frequency and percentage(%),the measurement data were expressed as mean±standard deviation((?)),?2 test were used for the genotype distribution differences between inter-group comparison,the genotypes of SNPrs1042725 locus were compared by one-way analysis of variance,two independent samples t-test was used for compare the genotypes of SNPrs7968682,P<0.05 was statistically significant.ResultsThere was no statistically significant difference in the genotype composition ratio and allele frequency between the two groups in the ISS group and the control group(P>0.05).The differences in GV before rhGH treatment between ISS and control group(rs1042725)were statistically significant(all P<0.05),Among them,children with the C allele had higher GV than T allele before treatment.After 1 year of rhGH treatment,the growth rate and IGF-1 level of ISS children increased significantly.After 1 year of rhGH treatment,the increase of height standard deviation score increase(?HtSDS)of GT genotype was higher than the TT genotype,and the difference was statistically significant(all P<0.05).ConclusionsThe polymorphism of HMGA2 gene SNPrs1042725 may be related to the height of preadolescent children,while the polymorphism of the SNPrs7968682 may be related to the efficacy of rhGH in ISS children. |
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