POLYMORPHIC ARYLAMINE N-ACETYLTRANSFERASE (NAT2) GENES IN CHILDREN WITH INSULIN-DEPENDENT DIABETES-MELLITUS

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-speci fic nested polymerase chain reaction, the NAT;2 genotypes were determi ned in 165 clinically well-controlled patients with IDDM and 107 refer ence 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 in stead of guanin) were distributed equally in both groups. Genotypes co ding fast acetylation (homozygous wildtype and heterozygous wild-type with one of the mutations) were detected in 40.6% and 36.6% of childre n 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 re ference children the NAT2 genotype was checked by conventional sulfame thazine (sulfadimidine) phenotyping. There were only five discrepant c ases, indicating that NAT2 genotyping enables correct prediction of NA T2 phenotype in about 95% of tested individuals. The fast acetylator g enotype could not be established as a host factor for IDDM susceptibil ity in children.