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.
['Marzuillo|Pierluigi|P|', 'Di Sessa|Anna|A|', 'Umano|Giuseppina Rosaria|GR|', 'Nunziata|Luigia|L|', 'Cirillo|Grazia|G|', 'Perrone|Laura|L|', 'Miraglia Del Giudice|Emanuele|E|', 'Grandone|Anna|A|']
D000293:Adolescent D000886:Anthropometry D001191:Arylamine N-Acetyltransferase D001786:Blood Glucose D002648:Child D002675:Child, Preschool D005260:Female D044882:Glucose Metabolism Disorders D006706:Homeostasis D006801:Humans D008297:Male D009765:Obesity
N-acetyltransferase 2 exaggerated plasma glucose excursion at 1 h insulin secretion glucose intolerance pediatric obesity