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Polymorphic arylamine N ‐acetyltransferase (NAT2) genes in children with insulin‐dependent diabetes mellitus
Author(s) -
Mrozikiewicz Przemyslaw M,
Drakoulis Nikolaos,
Roots Ivar
Publication year - 1994
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1994.187
Subject(s) - genotype , genotyping , odds ratio , allele , arylamine n acetyltransferase , diabetes mellitus , medicine , endocrinology , insulin , genetics , biology , gene
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 chain 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 cytosin at position 341 instead of thymin; M2 by adenin at 590 instead of guanin, M3 by adenin at 857 instead of guanin) 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. Clinical Pharmacology and Therapeutics (1994) 56, 626–634; doi: 10.1038/clpt.1994.187