特发性矮小生长激素受体外显子3基因多态性与生长激素轴的关系

摘要： 目的 探讨生长激素受体 （GHR） 外显子 3 基因型与特发性矮小 （ISS） 患者生长激素-胰岛素样生长因子- 胰岛素样生长因子结合蛋白 （GH-IGFs-IGFBPs） 轴的关系。方法 选取 108 例 ISS 儿童， 提取外周血 DNA 并采用多重 PCR 法进行 GHR 外显子 3 基因分型， 根据基因型结果分为 GHRfl 组和 GHRd3 组。测量 2 组身高、 体质量， 并计算体质指数 （BMI） 及 BMI 标准差计分 （SDS）； 测定空腹胰岛素样生长因子(IGF)-1、 胰岛素样生长因子结合蛋白（IGFBP） -3， 计算 IGF-1 SDS、 IGFBP3 SDS； 同时进行生长激素激发试验， 测定血清 GH 峰值。108 例中选取 55 例自愿接受重组人生长激素rhGH， 0.15 IU/ （kg·d） ]治疗 3 个月， 分析基因型与 rhGH 治疗后 IGF-1 水平的关系。结果 108 例 ISS 中 GHRfl 63 例， GHRd3 45 例。2 组间 BMI、 IGF-1、 IGFBP3、 GH 峰值以及 IGF-1 SDS、 IGFBP3 SDS 差异均无统计学意义(均 P > 0.05)； 多元逐步回归分析示年龄、 IGFBP3、 lg （BMI）、 lg （GH 峰值） 是 lgIGF-1 的影响因素 （均 P < 0.05）； 55例接受rhGH治疗ISS中GHRd3组 （34例） IGF-1和IGF-1 SDS治疗前后差值 （△IGF-1,△IGF-1 SDS） 高于 GHRfl组 （21例）。结论 ISS儿童GHR外显子3基因多态性可能与IGF-1及IGFBP3水平无关， 与GH敏感性有关。

Association of serum components of GH axis with GHR exon 3 polymorphism in idiopathic short stature children

Abstract： Objective To investigate the possible association of circulating components of GH-IGFs-IGFBPs system with the GHR-exon 3 genotype in idiopathic short stature (ISS) children. Methods Genomic DNA was extracted and isolat? ed from peripheral leukocytes in 108 ISS children. GHR-exon 3 polymorphism was analyzed with multiplex poly- merase chain reactions (PCR) assay. According to the results of genotype, ISS children were divided into GHRfl group and GHRd3 group. The height and weight were recorded in two groups. The body mass index (BMI) and BMI standard deviation score (SDS) were measured. The serum levels of insulin-like growth factor (IGF) -1, IGF-binding protein (IGFBP)-3, IGF-1 SDS and IGFBP3 SDS were calculated. GH stimulation test was used to measure the serum GH peak value. Fifty-five ISS chil? dren were treated with recombine human GH 0.15 IU/(kg·d)] for three months to analyse the association of IGF-1 responseof GH treatment and genotypes. Results There were 63 GHRfl and 45 GHRd3 in 108 ISS children. There were no signifi? cant differences in BMI, IGF-1, IGFBP3, GH peak, IGF-1 SDS and IGFBP3 SDS between two groups (P > 0.05). Multiple stepwise regression analysis showed that age, IGFBP3, lg (BMI) and lg (GH peak) were influencing factors of lgIGF-1 (P < 0.05). In 55 ISS children treated with rhGH, there were 34 cases of GHRd3. The differences of △IGF-1 and △IGF-1 SDS were higher in GHRd3 group than those of GHRfl group (n=21). Conclusion The GH sensitivity may be a risk factor in ISS children, which may not be related with GHR polymorphism.