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

Özet

Objective: In small for gestational age (SGA) children, catch-up growth could be influenced by methylation of several genes involvedin metabolism. Epigenetics 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.Methods: Observational prospective study of SGA children. Demographical and clinical variables were collected from clinical recordsand parents’ questionnaire. Methylation status of LEP, IRS2, and GLP2R promoters was evaluated in DNA extracted from patient andone parent saliva samples.Results: Forty-eight SGA patients were included. Twenty-six (54.2%) had catch-up growth phenotype and 22 (45.8%) did not. Themedian 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-upgroup. Catch-up patients had significantly larger waist circumference compared to non-catch-up group (median 55 cm [RIC 52-58] versusmedian 49.5 cm [RIC46-52]; p<0.001). LEP and GLP2R were methylated in all samples. IRS2 was methylated in 60% of SGA patientswithout difference between groups (p=0.520).Conclusion: There is no association between IRS2 methylation and catch-up growth among SGA patients. LEP and GLP2R weremethylated in all SGA patients. Gene methylation may be implicated in metabolic disease later in life. More studies should be performedto confirm this hypothesis.