生长激素释放肽基因多态性与青春期前特发矮小患儿重组人生长激素治疗疗效的关系研究

Analysis of the relationship between the polymorphism of growth hormone releasing peptide gene and the therapeutic effect of recombinant human growth hormone in children with prepuberty idiopathic short stature

目的 探讨生长激素释放肽(Ghrelin)基因多态性与青春期前特发矮小患儿重组人生长激素(rhGH)治疗疗效的关系。方法 我院儿童保健科门诊诊治的特发性矮小症儿童及青少年48例作为研究组,选取同期来我院体检的健康儿童48例作为对照组。采集受试儿童的静脉血,PCR扩增Ghrelin基因rs696217和rs26312位点目的片段,使用测序仪进行测序,对比两组Ghrelin基因rs696217和rs26312位点的多态性,并分析不同基因型特发矮小患儿治疗前和治疗1年后的生长速率(GV)、年龄对应身高标准差积分(HtSDSca)、骨龄身高标准差积分(HtSDSba)、生长因子结合蛋白3 (IGFBP3)和胰岛素样生长因子1(IGF-1)水平。结果 特发矮小组的身高、体重、BAI、BAD、IGF-1和IGFBP-3水平明显低于对照组(P<0.05);对照组和特发矮小组rs696217位点和rs26312位点基因分布情况比较差异无统计学意义(P>0.05);特发矮小组中Ghrelin基因rs696217和rs26312位点不同基因型的生长速率明显低于对照组(P<0.05);rs696217位点中GT、TT基因型是特发矮小患病的危险因素(P<0.05);特发矮小组患儿Ghrelin rs696217基因型CC中GV、IGFBP-3和IGF-1水平明显高于CA型和AA型(P<0.05),HtSDSca、HtSDSb比较差异无统计学意义(P>0.05);特发矮小组患儿Ghrelin rs26312各基因型中GV、HtSDSca、HtSDSb、IGFBP-3和IGF-1水平比较差异无统计学意义(P>0.05)。结论 Ghrelin基因rs696217位点GT、TT型与特发性矮小发病及rhGH的疗效相关,对临床rhGH治疗青春期前特发矮小具有一定的指导意义。

Objective To explore the relationship between the polymorphism of growth hormone releasing peptide(Ghrelin) gene and the therapeutic effect of recombinant human growth hormone(rhGH) in children with prepuberty idiopathic short stature.Methods Forty-eight children and adolescents with idiopathic dwarfism diagnosed and treated in the outpatient department of our hospital were selected as a study group, and 48 healthy children who came to our hospital for physical examination in the same period were selected as a control group. The venous blood of the children was collected. The target fragments of the Ghrelin gene rs696217 and rs26312 were amplified by PCR, and sequenced with a sequencer. The polymorphisms of the Ghrelin gene rs696217 and rs26312 were compared between the two groups. The growth rate(CGV), age-related height standard deviation score(HtSDSca), bone age height standard deviation score(HtSDSba) and the levels of growth factor binding protein 3(IGFBP3) and insulin-like growth factor 1(IGF-1)before and after 1 year of treatment were analyzed.Results The height, weight, and levels of BAI, BAD, IGF-1 and IGFBP-3 in the idiopathic short group were significantly lower than those in the control group(P<0.05). There was no significant difference in the gene distribution of rs696217 and rs26312 between the two groups(P>0.05). The growth rate of different genotypes at rs696217 and rs26312 of Ghrelin gene in idiopathic short group was significantly lower than that in the control group(P<0.05). GT and TT genotypes in rs696217 locus were risk factors for idiopathic short stature(P<0.05). The levels of GV, IGFBP-3 and IGF-1 in Ghrelin rs696217 genotype CC were significantly higher than those in CA and AA genotypes(P<0.05). There was no significant difference between HtSDSca and HtSDSb(P>0.05). There was no significant difference in the levels of GV, HtSDSca, HtSDSb, IGFBP-3 and IGF-1 among the genotypes of Ghrelin rs26312 in the idiopathic short group(P>0.05).Conclusions GT and TT types at rs696217 of Ghrelin gene are related to the onset of idiopathic short stature and the efficacy of rhGH. This has a certain guiding significance for clinical rhGH treatment of pre-adolescent idiopathic short stature.