Objective:To investigate the association between single nucleotide polymorphism (SNP) of eukaryotic translation initiation factor 2-α kinase 3 (EIF2AK3) gene in growth hormone deficiency (GHD), and to determine whether the polymorphisms in the EIF2AK3 of children with GHD associate with the efficacy of recombinant human growth hormone (rhGH) therapy.Methods:Five SNPs of EIF2AK3 gene, including rs1805165 (G>T), rs13045 (A>G), rs867529 (C>G), rs11684404 (T>C), rs6547787(T>G) were selected and genotyped by a TaqMan probe method in 104 children with GHD and 269 normal height control children. Among them, 55 children with GHD were treated with rhGH. The height and weight of each patient with GHD after rhGH treatment were collected. Finally, to investigate whether there were differences between the efficacy of rhGH in children with GHD and different genotypes of EIF2AK3 gene polymorphism.Results:(1) The polymorphisms rs13045 and rs867529 of EIF2AK3 gene were associated with the occurrence of GHD ( P<0.05). (2) The haplotypes GACTG and GAGTT composed of SNPs rs1805165, rs13045, rs867529, rs11684404, and rs6547787 of EIF2AK3 gene increased the risk of GHD with OR (95% CI) of 2.05 (1.33-3.17) and 2.62 (1.48-4.65), respectively. The haplotypes GACTT and TGCCG reduced the risk of GHD, with OR (95% CI) of 0.68 (0.48-0.97) and 0.36 (0.23-0.57), respectively. (3) After determination the relationship between different genotypes and efficacy of rhGH with rs13045 and rs867529, it was found that there was no significant difference in height gain between rs13045 genotypes after rhGH treatment ( P>0.05). Compared with CC genotype, there was a less height gain of CG genotype at rs867529 by 0.099 cm for every 30 d( β=-0.099, 95% CI -0.162--0.018, P=0.016). Conclusions:The EIF2AK3 gene polymorphism (rs13045, rs867529) was associated with the occurrence of GHD. The height gain of CG genotype of rs867529 was lower than that of CC genotype in children with GHD treated with rhGH. The EIF2AK3 locus rs867529 genotype was associated with rhGH efficacy.

Objective:To conduct a meta-analysis of clinical data to investigate the relationship between incretins and fracture in order to provide individualized hypoglycemic agents for type 2 diabetic patients with osteoporosis.Methods:PubMed, Embase, Web of Science, and Cochrane databases were searched up to January 1, 2018 for randomized controlled trials(RCTs)and the relationship between incretins and fracture was explored by meta-analysis.Results:The meta-analysis showed that the use of incretin was not associated with fracture risk compared with placebo or other positive hypoglycemic agents( OR 0.972, 95% CI 0.876-1.079). But in the subgroup analysis, 100 mg/d sitagliptin( OR 0.495, 95% CI 0.304-0.806)or 1.8 mg/d liraglutide( OR 0.621, 95% CI 0.413-0.933)reduced fracture risk. Conclusions:Meta-analysis shows no increase in the incidence of fracture events after the use of incretin. 100 mg/d sitagliptin or 1.8 mg/d liraglutide may exert protective effects on bone metabolism. However, the included data are from the reports of fracture adverse reactions in RCT studies, and large-scale clinical studies are needed to confirm these findings.