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

Abstract

Objective: In small for gestational age (SGA) children, catch-up growth could be influenced by methylation of several genes involved in 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 records and parents’ questionnaire. Methylation status of LEP, IRS2 , and GLP2R promoters was evaluated in DNA extracted from patient and one 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. 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 55 cm [RIC 52-58] versus median 49.5 cm [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). Conclusion: 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.

The effect of early life events on glucose levels in first-episode psychosis

“…Obstetric complications during gestation are associated with lower BW ( 39 ), while higher BW is associated with gestational diabetes (GDM). Methylation in several genes involved in metabolism, such as leptin or glucagon-like peptide receptors ( 40 ), or insulin-growing factors ( 41 ) have been described as potential pathways to explain the effect of low BW on later metabolic outcomes. Indeed, not only low BW but also GDM promote similar offspring methylation patterns, suggesting common genes and pathways linked to T2DM ( 42 ).…”