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