Relationship Between EIF2AK3 Gene Polymorphism And The Efficacy Of Recombinant Human Growth Hormone In Children With Growth Hormone Deficiency

Objective: We investigate the association between single nucleotide polymorphism(SNP)of eukaryotic translation initiation factor 2-alpha kinase 3 gene(EIF2AK3)in growth hormone deficiency(GHD),and determine whether the polymorphisms in the EIF2AK3 of children with GHD associate with the efficacy of recombinant human growth hormone(rhGH)therapy.Methods: In this study,104 children with GHD diagnosed in the department of endocrinology,affiliated hospital of jining medical university from January 2016 to June 2017,and 269 children with normal height at the same time in the pediatric surgery were selected.Five SNPs of the EIF2AK3 gene including rs1805165(G>T),rs13045(A>G),rs867529(C>G),rs11684404(T>C),rs6547787 were selected and genotyped by a TaqMan probe method.Among them,76 children with GHD were treated with rhGH.The height and weight of each patient with GHD after rhGH treatment were collected.To investigate whether there were difference between the efficacy of rhGH in children with GHD and different genotypes of EIF2AK3 gene polymorphism.Results: The polymorphisms rs13045 and rs867529 of EIF2AK3 gene were associated with the occurrence of GHD(P<0.05).The haplotypes GACTG and GAGTT composed of SNPs rs1805165,rs13045,rs867529,rs11684404 and rs6547787 of EIF2AK3 gene increased therisk 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.To determine the relationship between different genotypes and efficacy of rhGH with rs13045 and rs867529,and found that there was no significant difference in height gain between rs13045 genotypes after rhGH treatment(P>0.05).The height gain of rs867529 CG genotype was significantly better than CC genotype(P=0.011).Conlusions: The EIF2AK3 gene polymorphism(rs13045,rs867529)is 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 EFF2AK3 locus rs867529 genotype was associated with rhGH efficacy.