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.
Key words
Idiopathic short stature /
Ghrelin /
Liver-expressed antimicrobial peptide-2 /
Growth hormone secretagogue receptor /
Child
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References
1 王琳. 高度重视儿童矮身材的科学评估[J]. 中国当代儿科杂志, 2023, 25(11): 1095-1100. PMID: 37990451. PMCID: PMC10672958. DOI: 10.7499/j.issn.1008-8830.2308063.
2 刘舒慧, 占文君, 胡小娟, 等. 赖氨基醇B12、维生素D3联合重组人生长激素治疗矮小症的效果分析[J]. 中国现代医学杂志, 2023, 33(6): 77-81. DOI: 10.3969/j.issn.1005-8982.2023.06.014.
3 Ge X, Yang H, Bednarek MA, et al. LEAP2 is an endogenous antagonist of the ghrelin receptor[J]. Cell Metab, 2018, 27(2): 461-469.e6. PMID: 29233536. DOI: 10.1016/j.cmet.2017.10.016.
4 中华医学会儿科学分会内分泌遗传代谢学组, 《中华儿科杂志》编辑委员会; 梁雁. 基因重组人生长激素儿科临床规范应用的建议[J]. 中华儿科杂志, 2013, 51(6): 426-432. PMID: 24120059. DOI: 10.3760/cma.j.issn.0578-1310.2013.06.007.
5 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.
6 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.
7 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.
8 王凤云. 矮小儿童血清IGF-1、IGFBP3、GHBP及ghrelin水平及其与生长关系的研究[D]. 苏州: 苏州大学, 2009.
9 褚恩峰, 展翠萍. 血清ghrelin、LP及nesfatin-1在不同病因矮小症患儿中的表达[J]. 国际医药卫生导报, 2021, 27(20): 3227-3231. DOI: 10.3760/cma.j.issn.1007-1245.2021.20.029.
10 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.
11 解欣, 苏延, 王玉, 等. Ghrelin、Nesfatin-1与儿童矮小症的相关性研究[J]. 医学理论与实践, 2019, 32(19): 3048-3050. DOI: 10.19381/j.issn.1001-7585.2019.19.004.
12 高慧华. 特发性矮小症儿童血清ghrelin及IGF-1的变化与HP感染相关性的研究[D]. 苏州: 苏州大学, 2011.
13 刘亚萍, 汪晓霞, 郭丽格, 等. rhGH治疗儿科矮小症的临床价值分析[J]. 当代医学, 2021, 27(25): 88-90. DOI: 10.3969/j.issn.1009-4393.2021.25.035.
14 Xiao X, Bi M, Jiao Q, et al. A new understanding of GHSR1a: independent of ghrelin activation[J]. Ageing Res Rev, 2020, 64: 101187. PMID: 33007437. DOI: 10.1016/j.arr.2020.101187.
15 Els S, Beck-Sickinger AG, Chollet C. Ghrelin receptor: high constitutive activity and methods for developing inverse agonists[J]. Methods Enzymol, 2010, 485: 103-121. PMID: 21050913. DOI: 10.1016/B978-0-12-381296-4.00006-3.
16 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.
17 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.
18 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.
19 Zhao Q, Chu Y, Pan H, et al. Association between triglyceride glucose index and peak growth hormone in children with short stature[J]. Sci Rep, 2021, 11(1): 1969. PMID: 33479436. PMCID: PMC7820337. DOI: 10.1038/s41598-021-81564-2.
20 Mani BK, Puzziferri N, He Z, et al. LEAP2 changes with body mass and food intake in humans and mice[J]. J Clin Invest, 2019, 129(9): 3909-3923. PMID: 31424424. PMCID: PMC6715358. DOI: 10.1172/JCI125332.
21 Holm S, Husted AS, Skov LJ, et al. Beta-hydroxybutyrate suppresses hepatic production of the ghrelin receptor antagonist LEAP2[J]. Endocrinology, 2022, 163(6): bqac038. PMID: 35352108. PMCID: PMC9119693. DOI: 10.1210/endocr/bqac038.
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