河北医科大学学报 ›› 2025, Vol. 46 ›› Issue (3): 336-341.doi: 10.3969/j.issn.1007-3205.2025.03.015

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矮小症患儿EIF2AK3基因多态性特征及其与不同剂量生长激素治疗前后Ghrelin、Nesfatin-1、IGF-1及骨代谢指标变化的相关性研究

  

  1. 1.南京医科大学附属南京医院，南京市第一医院儿科，江苏 南京 210000；
    2.江苏省南京市秦淮区妇幼保健所儿保科，江苏 南京 210000

  • 出版日期:2025-03-25 发布日期:2025-03-27
  • 作者简介:苏聃（1981-），女，湖南湘谭人，南京医科大学附属南京医院，南京市第一医院主治医师，医学学士，从事儿科疾病诊治研究。

  • 基金资助:
    江苏省自然科学基金项目（BK20190597）

Characteristics of EIF2AK3 gene polymorphism in children with short stature and its correlation with changes in Ghrelin, Nesfatin-1, IGF-1 and bone metabolism indexes before and after treatment with different doses of growth hormone

  1. 1.Department of Pediatrics, Nanjing Hospital Affiliated to Nanjing Medical University, the First 
    Hospital of Nanjing City, Jiangsu Province, Nanjing 210000, China; 2.Department of 
    Children Care, Maternal and Child Health Care Institute of Qinhuai District 
    Jiangsu Province, Nanjing 210000, China

  • Online:2025-03-25 Published:2025-03-27

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摘要： 目的 探讨矮小症患儿真核翻译始动因子2-α激酶3(eukaryotic translation initiation factor 2-alpha kinase 3,EIF2aK3)基因多态性特征及其与不同剂量生长激素治疗前后饥饿素(Ghrelin)、人摄食抑制因子1(Nesfatin-1)、胰岛素样生长因子1（insulin-like growth factor-1，IGF-1）及骨代谢指标变化的相关性。
方法 选取矮小症患儿126例作为研究对象，采用信封法，将以上患儿随机分为A、B、C三组，另选取同期健康体检的志愿者126例作为对照组，A组采取的治疗剂量为0.26 mg/kg，B组采取的治疗剂量为0.35 mg/kg，C组采取的治疗剂量为0.41 mg/kg，分析矮小症患儿EIF2AK3基因多态性特征，分析不同剂量生长激素水平的Ghrelin、Nesfatin-1、IGF-1及骨代谢指标变化情况。
结果 通过对对照组和观察组的EIF2AK3基因多态性进行分析，观察组和对照组的EIF2AK3基因中的rs1805165、rs13045、rs867529、rs11684404的基因型和等位基因比较差异有统计学意义（P＜0.05），分析显示，rs1805165等位基因中的T、rs13045等位基因中的G、rs867529等位基因中的G、rs11684404等位基因中的C的突变均会造成矮小症的发病；3组治疗1年后的身高［(111.35±3.85) vs. (112.82±2.9) vs. (114.81±3.88)cm］、身高标准差［(2.37±0.82) vs. (1.86±0.77) vs. (1.56±0.78)］、生长速率［(8.09±3.17) vs. (9.22±3.03) vs. (11.11±3.89)cm/年］、骨龄［(10.49±3.61) vs. (10.8±3.79) vs. (11.75±2.88)岁］、身高增加值［(1.31±0.26) vs. (1.32±0.58) vs. (1.37±0.64)cm］、成年身高预测值［(155.75±3.07) vs. (158.4±3.75) vs. (160.99±3.07)cm］以及遗传靶身高［(156.57±2.54) vs. (159.01±2.59) vs. (161.49±2.49)cm］比较差异有统计学意义（P＜0.05），通过两两比较，3组随着使用生长激素剂量的升高，患者的身高、身高标准差、生长速率、骨龄、身高年龄、身高增加值、遗传靶身高以及成年身高预测值呈现显著的升高趋势，3组的Ghrelin、Nesfatin-1、IGF-1均显著改善，且随着治疗剂量的升高，患者的Ghrelin［(250.76±2.73) vs. (245.22±3.49) vs. (240.74±2.65)ng/L］显著降低，Nesfatin-1［(0.10±0.02) vs. (0.15±0.03) vs. (0.20±0.02)μg/L］、IGF-1［(218.35±3.87) vs. (227.23±3) vs. (300.09±3.97)μg/L］显著升高。
结论 矮小症患儿EIF2AK3基因多态性主要表现在rs1805165、rs13045、rs867529、rs11684404的突变，随着对患者的生长激素治疗剂量的升高，其治疗效果显著。


关键词: 侏儒症, EIF2AK3基因, 多态性

Abstract: Objective To investigate the characteristics of eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) gene polymorphism in children with short stature and its correlation with the changes in Ghrelin, Nesfatin-1, insulin-like growth factor-1 (IGF-1) and bone metabolism indexes before and after treatment with different doses of growth hormone. 
Methods In total, 126 patients with short stature were selected as research subjects. The envelope method was used to randomly divide the above patients into groups A, B and C, and 126 healthy volunteers undergoing physical examination during the same period were selected as control group. The therapeutic dose was 0.26 mg/kg in group A, 0.35 mg/kg in group B, and 0.41mg/kg in group C. The polymorphism characteristics of EIF2AK3 gene in children with short stature were analyzed, and the changes in GHRL, Nesfatin-1, IGF-1 and bone metabolism indexes treated with different doses of growth hormone were also analyzed. 
Results By analyzing the EIF2AK3 gene polymorphism in the control group and the observation group, it was found that there were significant differences in the genotypes and allele frequencies of rs1805165, rs13045, rs867529, and rs11684404 in the EIF2AK3 gene in both groups (P＜0.05). The analysis showed that mutations in T allele of rs1805165, G allele of rs13045, G allele of rs867529, and C allele of rs11684404 could lead to the onset of short stature. The differences in height ［(111.35±3.85) vs. (112.82±2.9) vs. (114.81±3.88) cm］, height standard deviation ［(2.37±0.82) vs. (1.86±0.77) vs. (1.56±0.78)］, growth rate ［(8.09±3.17) vs. (9.22±3.03) vs. (11.11±3.89) cm/year］, bone age ［(10.49±3.61) vs. (10.8±3.79) vs. (11.75±2.88) years］, height gain ［(1.31±0.26) vs. (1.32±0.58) vs. (1.37±0.64) cm］, predicted adult height ［(155.75±3.07) vs. (158.4±3.75) vs. (160.99±3.07) cm］, and genetic target height ［(156.57±2.54) vs. (159.01±2.59) vs. (161.49±2.49) cm］ after one year of treatment differed significantly among the three groups (P＜0.05). Through pairwise comparisons, it was found that as the dosage of growth hormone increased, the height, height standard deviation, growth rate, bone age, height age, height gain, predicted adult height and genetic target height of the patients in the three groups showed a significant upward trend. The GHRL, Nesfatin-1, and IGF-1 in all three groups improved significantly. Furthermore, with an increase in the doses of treatment, GHRL ［(250.76±2.73) vs. (245.22±3.49) vs. (240.74±2.65) ng/L］ decreased significantly while Nesfatin-1 ［(0.10±0.02) vs. (0.15±0.03) vs. (0.20±0.02) μg/L］ and IGF-1 ［(218.35±3.87) vs. (227.23±3) vs. (300.09±3.97) μg/L］ increased significantly in patients. 
Conclusion The polymorphism of EIF2AK3 gene in children with short stature is mainly manifested in rs1805165, rs13045, rs867529, rs11684404 mutations. With the increase of the dose of growth hormone for patients, its therapeutic effect is significant. 


Key words: short stature, EIF2AK3 genes, polymorphism

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