Novel association between the nonsynonymous A803G polymorphism of the N-acetyltransferase 2 gene and impaired glucose homeostasis in obese children and adolescents.

Background The N-acetyltransferase 2 ( NAT2) A803G polymorphism has been associated with decreased insulin sensitivity in a large adult population with the A allele associated with insulin-resistance-related traits. Objective Evaluate the association of this polymorphism with anthropometric and metabolic parameters in obese children and adolescents. Subjects A total of 748 obese children and adolescents were enrolled. Methods Anthropometric and laboratory data were collected. During oral glucose tolerance test, the presence of a possible exaggerated plasma glucose excursion at 1 h ( 1HPG) or impaired glucose tolerance ( IGT) was considered. Homeostasis model assessment, oral disposition index ( oDI) and insulinogenic index ( IDI) were calculated. 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 = .02 and P = .03). Moreover, this allele was associated with both oDI and IGI reduction ( P = .01). 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 ( P = .01). Children both homozygous and heterozygous for the A allele had higher risk to show elevated- 1HPG ( OR of 2.7, P = .005; and OR = 2.3, P = .005) compared with patients homozygous for the NAT2 803G allele. Conclusions 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 throughout an impairment of pancreatic β-cellular insulin secretion as suggested by oDI and IGI reduction. [ABSTRACT FROM AUTHOR]