Background: The N-acetyltransferase 2 (NAT2) A803G polymorphism leading to substitution of lysine to arginine at residue 268 and codifying for a cytosolic enzyme catalysing acetyl-CoA-dependent N- and O-acetylation reactions, has been associated with decreased insulin sensitivity in a large adult population with the A allele associated with insulin resistance (IR)-related traits.
Objective and hypotheses: We screened for this polymorphism, for the first time in literature, a population of obese children and adolescents and evaluated its association with anthropometrical and metabolic parameters.
Method: Seven hundred and forty-eight obese children and adolescents were enrolled. Anthropometrical and laboratory data were collected. IR was assessed using the homeostasis model assessment. All the patients underwent to an oral glucose tolerance test. Glycaemia at 60 to evaluate a possible exaggerated plasma glucose excursion at 1 h (1HPG) and at 120 minutes to evaluate a possible impaired glucose tolerance (IGT) were considered. Patients were genotyped for the NAT2 A803G polymorphism.
Results: The prevalence of both IGT and elevated-1HPG was higher in children carrying the A803 allele (P=0.02 and P=0.03, respectively). No differences among the NAT2 A803G genotypes for the other parameters were shown. Children homozygous for the A allele presented an odds ratio (OR), to show IGT of 4.9 (95% C.I. 1.318.5, P=0.01). Children both homozygous and heterozygous for the A allele had an higher risk to show elevated-1HPG (OR of 2.7 (95% C.I. 1.431.6, P=0.005) and OR=2.3 (95% C.I. 1.24.1, P=0.005 respectively)) compared to patients homozygous for the NAT2 803G allele.
Conclusion: NAT2 A803 allele seems to play a role in worsening the destiny of obese children carrying it, predisposing them to elevated-1HPG and IGT and then to a possible future type 2 diabetes mellitus.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology