Relationship Between Kiss-1 Gene Polymorphisms And The Efficacy Of Recombinant Human Growth Hormone(rhGH)Treatment In Children With Idiopathic Short Stature

Background Idiopathic short stature(ISS)is one of majority diseases in pediatric endocrine clinics center,accounting for 60%~80% of short stature.The pathogenesis of ISS has not been elucidated completely,it was influenced by nutrition,hormone,heritability and so on.The growth hormone-insulin like growth factor axis plays a significant role in the pathogenesis of ISS.The preferred treatment for ISS is recombinant human growth hormone(rh GH),but it is expensive and has different therapeutic effects.Growth is mainly regulated by the endocrine systems such as hypothalamicpituitary-growth hormone axis.The Kisspeptin(kiss)gene plays an essential role in the process of growth.Studies have found that in vitro the rat and bovine pituitary cells cultured with Kisspeptin(Kp)can promote GH secretion and increase serum GH concentration,and in vivo the mice knocking out the Kiss-1 gene will eventually grow into dwarf mice.There are no correlation study between Kiss-1 gene and pre-pubertal short stature children.ObjectiveThis study aimed to identify a possible correlation between Kiss-1 gene polymorphisms with pre-pubertal idiopathic short stature children and the efficacy of recombinant human growth hormone(rh GH)treatment.Methods 120 prepubertal children diagnosed with ISS(ISS group)and 120 healthy ageand gender-matched children of normal height(control group)in the Endocrine Diagnosis and Treatment Center of The Third Clinical College of Zhengzhou University were included.Two single nucleotide polymorphisms in the Kiss-1 gene(SNP rs3924587 and SNP rs12998)were typed.Genomic DNA was extracted from selected subjects for sequencing the C.-89SNP(rs3924587)and C.58SNP(rs12998)profile of Kiss-1 gene using the ABI3730 xl sequencer.ISS group treated with rh GH [0.35-0.42 mg /(kg.w)] more than 12 months.The growth velocity,bone age and serum insulin-like growth factor 1(IGF-1)levels were determined during the rh GH treatment.ResultsGenetic analysis indicated that there was not any polymorphism or mutation in control group and the rs3924587 SNP of ISS group.In ISS group,C.58 G>A was detected in 1 patient(girl)at the rs12998 SNP.There was no significant differences in the genotype frequencies in research objects.There was no significant difference in genotype composition ratio and allele frequency between the two groups in the ISS group and the control group(P>0.05).After 12 months of rh GH treatment,the growth rate of children in the ISS group increased significantly,but there was no significant difference in the growth rate of different genotypes in the ISS group(P>0.05).After 12 months of rh GH treatment,serum IGF-1 levels in the ISS group were not significantly different from those before treatment(P>0.05).ConclusionsThe Kiss-1 gene polymorphism was not significantly relate to the occurrence of ISS,but the above conclusions was influenced by factors such as small sample size and geographical differences.After rh GH treatment,the growth velocity of children in ISS group was significantly higher than that before treatment,but the growth rate was not significantly correlated with genotyping of rs3924587 and rs12998.There was no significantly relation between Kiss-1 gene polymorphism(rs3924587 and rs12998)and the growth-promoting effect of rh GH.