Original Article

Methylation Status of GLP2R, LEP and IRS2 in Small for Gestational Age Children with and Without Catch-Up Growth


  • Mario Angulo
  • Diana Ramirez-Montaño
  • Laura Torres-Canchala
  • Ximena García
  • Rodrigo Lemus
  • Ana M. Aristizabal
  • Danielle Floyd-Aristizábal
  • Diana M. Dávalos
  • Lorena Diaz-Ordoñez
  • Harry Pachajoa

Received Date: 22.04.2020 Accepted Date: 06.09.2020 J Clin Res Pediatr Endocrinol 0;0(0):0-0 [e-Pub] PMID: 32936762


In small for gestational age (SGA) children, catch-up growth could be influenced by several gene methylation involved in metabolic process. Epigenetic may influence the development of metabolic diseases in adulthood.


To compare the methylation of leptin (LEP), glucagon-like peptide-2 receptor (GLP2R), insulin receptor substrate-2 (IRS2) in SGA patients with and without catch-up growth.


Observational prospective study. We included 48 SGA patients. Demographical and clinical variables were collected from clinical records and parents’ questionnaire. Methylation status of LEP, IRS2, and GLP2R promoters was evaluated in DNA extracted from patient and one parent saliva samples.


Twenty-six (54.2%) patients had catch-up growth phenotype and 22 (45.8%) patients did not. The median age was 5.2 years [RIC 4.1-6.8] without difference between groups (p=0.306). The catch-up group had increased appetite (42.3% vs 9.1%, p=0.008), family history of dyslipidemia (42.3% vs. 27.3%) and diabetes (34.6% vs. 22.7%) compared to non-catch-up group. Catch-up patients had significantly larger waist circumference compared to non-catch-up group (median 55cm [RIC52–58] versus median 49.5cm, [RIC46-52] p<0.001). LEP and GLP2R were methylated in all samples. IRS2 was methylated in 60% of SGA patients without difference between groups (p=0.520).


There is no association between IRS2 methylation and catch-up growth among SGA patients. LEP and GLP2R were methylated in all SGA patients. Gene methylation may be implicated in metabolic disease later in life. More studies should be performed to confirm this hypothesis.

Keywords: Low birth weight; Infant, Small for gestational age; Epigenetics; Methylation, DNA; Insulin resistance