Brocvielle H, Muret P, Goydadin A-C, Boone P, Broly F, Kantelip J-P, Humbert P
Laboratoire d'Ingénierie et de Biologie Cutanées, Faculté de Médecine et de Pharmacie, Besançon, France.
Skin Pharmacol Appl Skin Physiol. 2003 Nov-Dec;16(6):386-92. doi: 10.1159/000072934.
The genetic polymorphism of human N-acetyltransferase 2 (NAT2) divides the human population into groups with rapid, intermediate and slow acetylator status. Slow acetylator status has been considered a predisposing factor for allergic diseases, lupus erythematosus, toxic epidermal necrolysis or Stevens-Johnson syndrome. The aim of this study was to investigate whether Caucasian patients suffering from atopic dermatitis differed from healthy individuals with regard to the genotype and phenotype of NAT2. Twenty unrelated healthy Caucasian volunteers (9 females and 11 males, aged from 22 to 59 years) and twenty unrelated Caucasian patients suffering from atopic dermatitis (9 females and 11 males, aged between 20 and 54 years) participated in this study. For each one, the NAT2 genotype was determined by polymerase chain reaction with DNA extracted from peripheral blood, using specific primers for the wild-type allele (wt) and the 3 most frequent mutated alleles of NAT2 (C481-->T, G590-->A and G857-->A). The NAT2 phenotype was evaluated with dapsone as a test substrate using high-pressure liquid chromatography. Statistical analysis was performed using the chi(2) test. Phenotype and genotype were distributed as follows: (1) of the healthy subjects, 60% were rapid acetylators (RA) and 40% were slow acetylators (SA); 10% of the RA and 15% of the SA were homozygous, 50% of the RA and 25% of the SA were heterozygous; (2) of the patients, 55% were RA, 40% were SA and 5% were intermediate acetylators (IA); 10% of the RA and 10% of the SA were homozygous, 45% of the RA and 35% of the SA were heterozygous. No significant statistical difference was found between the two groups for genotypes (p = 0.75) or phenotypes (p = 0.60). The phenotyping and genotyping results of healthy subjects were comparable to those found in previous studies. The absence of a significant statistical difference between healthy subjects and atopic dermatitis patients is in contrast to the results of previous studies. Some authors considered that allergic patients are mostly SAs. This could be explained by the fact that we only considered patients suffering from atopic dermatitis whereas, in other studies, patients suffered from different (one or several associated) allergic diseases. NAT2 polymorphism does not differ between patients suffering from atopic dermatitis and healthy subjects. The importance attributed to the SA status, which was previously considered a predisposing factor for allergic diseases such as atopic dermatitis, should be reviewed.
人类N - 乙酰基转移酶2(NAT2)的基因多态性将人群分为快速、中间和慢速乙酰化状态组。慢速乙酰化状态被认为是过敏性疾病、红斑狼疮、中毒性表皮坏死松解症或史蒂文斯 - 约翰逊综合征的易感因素。本研究的目的是调查患有特应性皮炎的白种人患者在NAT2的基因型和表型方面是否与健康个体存在差异。二十名无亲缘关系的健康白种人志愿者(9名女性和11名男性,年龄在22至59岁之间)和二十名无亲缘关系的患有特应性皮炎的白种人患者(9名女性和11名男性,年龄在20至54岁之间)参与了本研究。对于每一位受试者,使用针对野生型等位基因(wt)和NAT2的3种最常见突变等位基因(C481→T、G590→A和G857→A)的特异性引物,通过聚合酶链反应从外周血提取的DNA中确定NAT2基因型。以氨苯砜作为测试底物,采用高压液相色谱法评估NAT2表型。使用卡方检验进行统计分析。表型和基因型分布如下:(1)在健康受试者中,60%为快速乙酰化者(RA),40%为慢速乙酰化者(SA);RA中有10%为纯合子,SA中有15%为纯合子,RA中有50%为杂合子,SA中有25%为杂合子;(2)在患者中,55%为RA,40%为SA,5%为中间乙酰化者(IA);RA中有10%为纯合子,SA中有10%为纯合子,RA中有45%为杂合子,SA中有35%为杂合子。两组在基因型(p = 0.75)或表型(p = 0.60)方面均未发现显著统计学差异。健康受试者的表型分析和基因分型结果与先前研究中的结果相当。健康受试者和特应性皮炎患者之间不存在显著统计学差异,这与先前研究的结果相反。一些作者认为过敏患者大多是慢速乙酰化者。这可以解释为我们仅考虑了患有特应性皮炎的患者,而在其他研究中患者患有不同的(一种或几种相关的)过敏性疾病。患有特应性皮炎的患者与健康受试者之间的NAT2多态性没有差异。先前被认为是特应性皮炎等过敏性疾病易感因素的慢速乙酰化状态的重要性应重新审视。