Ghrelin Levels And Polymorphisms Of Ghrelin/Obestatin Gene In Zhejiang Chinese Children With Short Stature

Backgroundghrelin was identified as the endogenous ligand for growth hormone(GH) secretogogue(GHS)receptor(GHSR)type la and has endocrine,orexigenic,and gastrointestinal effects.Recently,Stanford University biologists reported that a 23-amino acid peptide named obestatin was also produced by posttranslational modification of the ghrelin precursor,and it might have an opposite ghrelin's effect on food intake.Hence,this gene should be called as ghrelin/obestatin gene as it has twinborn productions.Like other GHSs,ghrelin can activate its receptor and stimulate GH secretion from the pituitary gland.Some studies suggested ghrelin-GHSR increased GH secretion by stimulated GH relating hormone(GHRH)secretion in hypothalamus and GH secretion directly in pituitary gland,but the accurate mechanism of ghrelin in regulating GH synthesis and/or secretion was not full understood yet.Moreover,only several studies about the ghrelin level in adults with short stature were reported with discrepant results.Three single nucleotide polymorphisms of ghrelin/obestatin gene (SNPs)in exon,including Arg51Gln,Leu72Met and Gln90Leu,have been reported recently.The relationships between these SNPs and obesity,diabetes,bulimia nervosa, anorexia,and breast cancer have been investigated in several studies.However,to our knowledge,no similar study about these SNPs in children with short stature was reported.Investigating the relationship between the ghrelin/obestatin SNPs and short stature statue might help us to fully understand the physiological effect of ghrelin and obestatin,especially their effect on children's growth. ObjectivesTo investigate the role of ghrelin and obestatin on GHRG-GH axis by measuring the ghrelin level and detecting the ghrelin/obestatin gene polymorphism in short stature children.MethodsA total of 117 growth hormone deficiency(GHD)and 81 idiopathic short stature(ISS) children were enrolled.The controls consisted of 125 age and gender-match healthy children.The Arg51Gln,Leu72Met and Gln90Leu polymorphisms were genotyped using MassArray and plasma ghrelin levels were measured by radioimmunoassay.Results1.The plasma ghrelin levels of GHD group were significantly lower than those of controls(P=0.001).2.The frequencies of Arg51Gln polymorphism was very lower(0 in controls and 1.00%in patients).The frequencies of Gln90Leu polymorphism were 1.60%in controls and 0.50%in patients respectively.Higher frequencies of Leu72Met (34.4%in controls and 39.9%in patients)and Met72Met genotypes(4.00%in controls and 2.02%in patients)were found.3.The differences of Arg51Gln,Leu72Met or Gln90Leu genotype and allele frequencies between patients and controls was not significant(P＞0.05 respectively).4.There were no significant difference in the Leu72Met genotype and allele frequencies between GHD and ISS subgroups was noted as well(P＞0.05, respectively).Moreover,no significant difference of clinical characteristics and biochemistry markers(including ghrelin levels)was found among different genotypes of Leu72Met(P＞0.05,respectively). Conclusion1.The plasma ghrelin levels of GHD group were significantly lower than those of controls.2.The differences of Arg51Gln,Leu72Met or Gln90Leu genotype and allele frequencies between patients and controls was not significant3.Lower ghrelin levels,but not ghrelin/obestatin polymorphism,might be a reason of GHD.