Association Of Single Nucleotide Polymorphism Of BBF2H7 Gene With Levels Of IGF-1 And Efficacy Of Recombinant Human Growth Hormone In Children With Growth Hormone Deficiency

Objective: The genetic analysis of the etiology of growth hormone deficiency(GHD)in children was carried out.To explore the relationship between single nucleotide polymorphism(SNP)of BBF2 human homolog on chromosome 7(BBF2H7)gene in endoplasmic reticulum stress(ERS)and the concentration of insulin-like growth factor(IGF-1)and the therapeutic effect of recombinant human growth hormone(rhGH).Methods: From January 2016 to June 2017,104 children with GHD were hospitalized in the Department of Endocrinology,Affiliated Hospital of Jining Medical College,and 269 normal-height children were hospitalized in pediatric surgery of our hospital during the same period.76 of 104 children in the GHD group received rhGH treatment.The clinical data of the subjects were collected,including basic information,biochemical indicators,imaging examinations and genomic DNA was extracted for laboratory research.BBF2H7 loci in two ERS,rs273957 and rs66593747,were detected and analyzed by Taqman probe technique.BBF2H7 loci in GHD group and healthy control group were compared,and the relationship between the polymorphism of BBF2H7 loci and the level of IGF-1 in children with GHD and the efficacy of rhGH was observed.Results: The frequency of BBF2H7 loci rs273957 SNP was 19.78% in the control group and 14.42% in the GHD group.Homozygous mutations werefound 0.37% in the control group and 0.96% in the GHD group.The frequency of BBF2H7 loci rs66593747 SNP was 28.95% in the control group and 30.30%in the GHD group.Homozygous mutations were found 4.14% in the control group and 7.07% in the GHD group.The SNP of BBF2H7 loci rs273957 and rs66593747 were not correlated with GHD(P>0.05),and there was no correlation between the polymorphisms of BBF2H7 loci and the concentration of IGF-1 in children with GHD(P>0.05).Analyzing the relationship between different genotypes of rs273957 and rs66593747 loci and therapeutic effect,we found that there was no significant difference in height growth among rs273957 genotypes after rhGH treatment(P>0.05).The height and length of GT genotype at rs66593747 locus were significantly better than that of GG genotype(P=0.044).Conclusions: The polymorphisms of rs273957 and rs66593747 in endoplasmic reticulum stress BBF2H7 loci were not associated with GHD.There was no correlation between the polymorphism of GHD loci and the concentration of IGF-1.Compared with GG genotype,GT genotype of BBF2H7 polymorphism locus rs66593747 increased the therapeutic effect.That is,the height growth of GT genotype was better in GHD children after rhGH treatment than that of GG genotype.The GT genotype at rs66593747 locus can be used as one of the predictors of good therapeutic effect of rhGH.