Abstract:Objective To investigate the expression levels of ghrelin and liver-expressed antimicrobial peptide-2 (LEAP-2) in children with idiopathic short stature (ISS) to provide reference for further understanding the etiology of short stature. Methods A prospective study was conducted from December 2021 to October 2023, involving 46 children diagnosed with ISS (ISS group) and 46 healthy children with normal height (control group) at the First Affiliated Hospital of Shihezi University. General data and serum levels of ghrelin and LEAP-2 were compared between the two groups. The predictive value of these two indicators for ISS was evaluated using receiver operating characteristic (ROC) curve analysis. Results The serum level of ghrelin in the ISS group was higher than that in the control group, while the level of LEAP-2 was lower (P<0.05). The ratio of LEAP-2 to ghrelin was lower in the ISS group compared to the control group (P<0.05). Multivariate logistic regression analysis showed that HtSDS, IGF-1, ghrelin, LEAP-2, and the ratio of LEAP-2/ghrelin were independently associated with the occurrence of ISS (P<0.05). ROC curve analysis indicated that the AUCs for ghrelin, LEAP-2, the ratio of ghrelin to LEAP-2, and their combination in predicting ISS were all >0.8. The optimal cutoff values for ghrelin, LEAP-2, and the LEAP-2/ghrelin ratio were 5 607 pg/mL, 1 155 pg/mL, and 0.212, respectively. In children with ISS, ghrelin showed a negative correlation with chronological age, LEAP-2, and the LEAP-2/ghrelin ratio (P<0.05), while it was positively correlated with growth rate and peak growth hormone levels (P<0.05). LEAP-2 was negatively correlated with growth rate, peak growth hormone levels, and ghrelin (P<0.05), but positively correlated with chronological age and the LEAP-2/ghrelin ratio (P<0.05). Conclusions Ghrelin and LEAP-2 are correlated with the occurrence of ISS, which may provide references for the diagnosis and etiological analysis of children with ISS.
LIU Qing,ZHANG Wei-Chun,CHEN Bo et al. Correlation between serum ghrelin and liver-expressed antimicrobial peptide-2 with idiopathic short stature in children[J]. CJCP, 2024, 26(12): 1261-1266.
Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach[J]. Nature, 1999, 402(6762): 656-660. PMID: 10604470. DOI: 10.1038/45230.
Mosa RM, Zhang Z, Shao R, et al. Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases[J]. Endocrine, 2015, 49(2): 307-323. PMID: 25645463. DOI: 10.1007/s12020-015-0531-z.
Arvat E, Maccario M, Di Vito L, et al. Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans: comparison and interactions with hexarelin, a nonnatural peptidyl GHS, and GH-releasing hormone[J]. J Clin Endocrinol Metab, 2001, 86(3): 1169-1174. PMID: 11238504. DOI: 10.1210/jcem.86.3.7314.
Camurdan MO, Bideci A, Demirel F, et al. Serum ghrelin, IGF-I and IGFBP-3 levels in children with normal variant short stature[J]. Endocr J, 2006, 53(4): 479-484. PMID: 16820702. DOI: 10.1507/endocrj.k05-167.
M'Kadmi C, Cabral A, Barrile F, et al. N-terminal liver-expressed antimicrobial peptide 2 (LEAP2) region exhibits inverse agonist activity toward the ghrelin receptor[J]. J Med Chem, 2019, 62(2): 965-973. PMID: 30543423. DOI: 10.1021/acs.jmedchem.8b01644.
Barja-Fernández S, Lugilde J, Castelao C, et al. Circulating LEAP-2 is associated with puberty in girls[J]. Int J Obes (Lond), 2021, 45(3): 502-514. PMID: 33139887. DOI: 10.1038/s41366-020-00703-3.
Labarthe A, Tolle V. Ghrelin: a gastric hormone at the crossroad between growth and appetite regulation[J]. Biol Aujourdhui, 2016, 210(4): 237-257. PMID: 28327282. DOI: 10.1051/jbio/2016027.