title: N-acetyltransferase 1 and 2 polymorphisms in para-substituted arylamine-induced contact allergy.
abstract: Sensitization to arylamines such as p-phenylenediamine is frequently diagnosed in patients with allergic contact dermatitis. Reactive metabolites of p-phenylenediamine might be produced in the skin by O-acetylation of N-hydroxylamines catalysed by local N-acetyltransferases (NATs). In this study, we tested whether genetic polymorphisms of NATs, which are known to affect enzyme activity, may influence the susceptibility to para-substituted arylamine-induced contact eczema. Using polymerase chain reaction and restriction enzyme analysis, the distribution of polymorphisms of NAT1 and NAT2 was investigated in 88 patients sensitized to para-substituted aryl compounds and 123 healthy controls. NAT2 rapid acetylators, i.e. carriers of the NAT2*4 wild-type allele, were more common in the contact allergy (44%) than in the healthy control group [30%; P = 0.042, odds ratio 1.9 (95% confidence interval, CI 1. 05-3.27)]. Slow acetylators carrying the NAT2*5b/2*6a genotype were significantly less frequent among patients [13% vs. 38% in controls; P = 0.009, odds ratio 0.39 (95% CI 0.19-0.78)]. The carriage rate of the NAT1*10 allele, which is supposed to encode for a rapid NAT1 phenotype, was not significantly different between patients and controls [43% vs. 36%; odds ratio 1.5 (95% CI 0.88-2.68)]. Interactions between NAT2*4 and NAT1*10 were suggested by the increased frequency of the NAT2*4/NAT1*10 haplotype in patients (27%) compared with controls [15%; P = 0.039, odds ratio 2.1 (95% CI 1.04-4.04)]. As the NAT1 and NAT2 encoding genes are located in close proximity on chromosome 8p22, the latter finding could at least partly be due to genetic linkage. In fact, a linkage disequilibrium between NAT2*4 and NAT1*10 was observed in the contact allergy (P = 0.0025) and in the control group (P = 0.042). Our data indicate an association between the NAT2*4/NAT1*10 haplotype and contact sensitization to para-substituted aryl compounds. Therefore, acetylation may either enhance contact sensitization or NAT2*4 and NAT1*10 might be linked to an unknown susceptibility factor.
authors.affiliation: Department of Occupational Health, Georg-August-University, Waldweg 37, D-37073 Göttingen, Germany.
authors.forename: G A
authors.initials: GA
authors.lastname: Westphal
authors.forename: K
authors.initials: K
authors.lastname: Reich
authors.forename: T G
authors.initials: TG
authors.lastname: Schulz
authors.forename: C
authors.initials: C
authors.lastname: Neumann
authors.forename: E
authors.initials: E
authors.lastname: Hallier
authors.forename: A
authors.initials: A
authors.lastname: Schnuch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D003877:Dermatitis, Contact / Q000209:etiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D007527:Isoenzymes; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human