N-acetyltransferase 1 and 2 polymorphisms in para-substituted arylamine-induced contact allergy

Sensitization to arylamines such as p-phenylenediamine is frequently diagno sed in patients with allergic contact dermatitis, Reactive metabolites of p -phenylenediamine might be produced in the skin by O-acetylation of N-hydro xylamines catalysed by local iv-acetyltransferases (NATs). in this study we tested whether genetic polymorphisms of NATs, which are known to affect en zyme activity, may influence the susceptibility to para-substituted arylami ne-induced contact eczema, Using polymerase chain reaction and restriction enzyme analysis, the distribution of polymorphisms of NAT1 and NAT2 was inv estigated in 88 patients sensitized to para-substituted aryl compounds and 123 healthy controls. NAT2 rapid acetylators, i.e. carriers of the NAT2*4 w ild-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 inter val, CI 1.05-3.27)]. Slow acetylators carrying the NAT2*5b/2*6a genotype we re 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 ra tio 1.5 (95% CI 0.88-2.68)]. Interactions between NAT2*4 and NAT1*10 were s uggested by the increased frequency of the NAT2*4/NAT1*10 haplotype in pati ents (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 proxim ity 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 grou p (P = 0.042). Our data indicate an association between the NAT2*4/NAT1*10 haplotype and contact sensitization to pal a-substituted aryl compounds. Th erefore, acetylation may either enhance contact sensitization or NAT2*4 and NAT1*10 might be linked to an unknown susceptibility factor.