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  • Title: Polymorphic arylamine N-acetyltransferase (NAT2) genes in children with insulin-dependent diabetes mellitus.
    Author: Mrozikiewicz PM, Drakoulis N, Roots I.
    Journal: Clin Pharmacol Ther; 1994 Dec; 56(6 Pt 1):626-34. PubMed ID: 7995004.
    Abstract:
    Polymorphic liver arylamine N-acetyltransferase (NAT2; EC 2.3.1.5) has been suggested as a susceptibility factor for both insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus. Previous studies reported an overrepresentation of phenotypically fast acetylators among patients with diabetes. With use of an allele-specific nested polymerase reaction, the NAT2 genotypes were determined in 165 clinically well-controlled patients with IDDM and 107 reference children aged from 3 to 18 years. Wild-type and mutated alleles (mutation 1 diagnosed by presence of cytosine at position 341 instead of thymine; M2 by adenine at 590 instead of guanine, M3 by adenine at 857 instead of guanine) were distributed equally in both groups. Genotypes coding fast acetylation (homozygous wild-type and heterozygous wild-type with one of the mutations) were detected in 40.6% and 36.6% of children with IDDM and reference children, respectively (odds ratio, 1.19; 95% confidence limits, 0.70 to 2.04). In 66 children with IDDM and 54 reference children the NAT2 genotype was checked by conventional sulfamethazine (sulfadimidine) phenotyping. There were only five discrepant cases, indicating that NAT2 genotyping enables correct prediction of NAT2 phenotype in about 95% of tested individuals. The fast acetylator genotype could not be established as a host factor for IDDM susceptibility in children.
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