Novel association between the nonsynonymous A803G polymorphism of the N‐acetyltransferase 2 gene and impaired glucose homeostasis in obese children and adolescents. Issue 6 (2nd August 2016)

• Record Type: Journal Article
• Authors: Marzuillo, Pierluigi; Di Sessa, Anna; Umano, Giuseppina Rosaria; Nunziata, Luigia; Cirillo, Grazia; Perrone, Laura; Miraglia del Giudice, Emanuele; Grandone, Anna
• Is Part Of: Pediatric diabetes. Volume 18:Issue 6(2017)
• Page Start: 478
• Page End: 484
• Publication Date: 2016-08-02
• Subjects: exaggerated plasma glucose excursion at 1 h -- glucose intolerance -- insulin secretion -- N‐acetyltransferase 2 -- pediatric obesity; Diabetes in children -- Periodicals; 616.462
• DOI: 10.1111/pedi.12417
• Languages: English
• ISSNs: 1399-543X

Abstract

Abstract : 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.