Westphal G A, Reich K, Schulz T G, Neumann C, Hallier E, Schnuch A
Department of Occupational Health, Georg-August-University, Waldweg 37, D-37073 Göttingen, Germany.
Br J Dermatol. 2000 Jun;142(6):1121-7. doi: 10.1046/j.1365-2133.2000.03536.x.
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 NAT24 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 NAT25b/26a 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 NAT110 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 NAT24 and NAT110 were suggested by the increased frequency of the NAT24/NAT110 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 NAT24 and NAT110 was observed in the contact allergy (P = 0.0025) and in the control group (P = 0.042). Our data indicate an association between the NAT24/NAT110 haplotype and contact sensitization to para-substituted aryl compounds. Therefore, acetylation may either enhance contact sensitization or NAT24 and NAT110 might be linked to an unknown susceptibility factor.
对诸如对苯二胺等芳基胺类物质敏感，在过敏性接触性皮炎患者中经常被诊断出来。对苯二胺的反应性代谢产物可能在皮肤中由局部N - 乙酰转移酶（NATs）催化的N - 羟胺的O - 乙酰化产生。在本研究中，我们测试了已知会影响酶活性的NATs基因多态性是否可能影响对对位取代芳基胺诱导的接触性湿疹的易感性。使用聚合酶链反应和限制性酶切分析，研究了88例对对位取代芳基化合物敏感的患者和123名健康对照中NAT1和NAT2多态性的分布情况。NAT2快速乙酰化者，即NAT24野生型等位基因的携带者，在接触性过敏患者中更为常见（44%），高于健康对照组[30%；P = 0.042，优势比1.9（95%置信区间，CI 1.05 - 3.27）]。携带NAT25b/26a基因型的慢乙酰化者在患者中显著较少见[患者中为13%，对照组中为38%；P = 0.009，优势比0.39（95%CI 0.19 - 0.78）]。推测编码快速NAT1表型的NAT110等位基因的携带率在患者和对照组之间无显著差异[43%对36%；优势比1.5（95%CI 0.88 - 2.68）]。与对照组[15%；P = 0.039，优势比2.1（95%CI 1.04 - 4.04）]相比，患者中NAT24/NAT110单倍型的频率增加，提示NAT24与NAT110之间存在相互作用。由于NAT1和NAT2编码基因在8号染色体p22上位置紧密相邻，后一发现至少部分可能是由于基因连锁。事实上，在接触性过敏患者（P = 0.0025）和对照组（P = 0.042）中均观察到NAT24与NAT110之间存在连锁不平衡。我们的数据表明NAT24/NAT110单倍型与对对位取代芳基化合物的接触致敏之间存在关联。因此，乙酰化可能增强接触致敏，或者NAT24和NAT110可能与一个未知的易感因素相关联。
