BACKGROUND: Para-phenylenediamine (PPD) is a common contact sensitizer causing allergic contact dermatitis, a major skin problem. As PPD may need activation to become immunogenic, the balance between activation and/or detoxification processes may influence an individual's susceptibility. PPD is acetylated and the metabolites do not activate dendritic-like cells and T cells of PPD-sensitized individuals. OBJECTIVES: To investigate whether PPD can be acetylated in vitro by the two N-acetyltransferases 1 (NAT1) and 2 (NAT2). Based on the assumption that N-acetylation by NAT1 or NAT2 is a detoxification reaction with respect to sensitization, we examined whether NAT1 and NAT2 genotypes are different between PPD-sensitized individuals and matched controls. METHODS: Genotyping for NAT1 and NAT2 polymorphisms was performed in 147 PPD-sensitized individuals and 200 age- and gender-matched controls. Results Both PPD and monoacetyl-PPD were N-acetylated in vitro by recombinant human NAT1 and to a lesser extent by NAT2. Genotyping for NAT1*3, NAT1*4, NAT1*10, NAT1*11 and NAT1*14 showed that genotypes containing the rapid acetylator NAT1*10 allele were under-represented in PPD-sensitized cases (adjusted odds ratio 0.72, 95% confidence interval 0.45-1.16). For NAT2, NAT2*4, NAT2*5AB, NAT2*5C, NAT2*6A and NAT2*7B alleles were genotyped. Individuals homozygous for the rapid acetylator allele NAT2*4 were under-represented in cases compared with controls (4.3% vs. 9.4%), but this trend was not significant. CONCLUSIONS: With respect to data indicating that NAT1 but not NAT2 is present in human skin, we conclude that NAT1 genotypes containing the rapid acetylator NAT1*10 allele are potentially associated with reduced susceptibility to PPD sensitization.
BACKGROUND:Para-phenylenediamine (PPD) is a common contact sensitizer causing allergic contact dermatitis, a major skin problem. As PPD may need activation to become immunogenic, the balance between activation and/or detoxification processes may influence an individual's susceptibility. PPD is acetylated and the metabolites do not activate dendritic-like cells and T cells of PPD-sensitized individuals. OBJECTIVES: To investigate whether PPD can be acetylated in vitro by the two N-acetyltransferases 1 (NAT1) and 2 (NAT2). Based on the assumption that N-acetylation by NAT1 or NAT2 is a detoxification reaction with respect to sensitization, we examined whether NAT1 and NAT2 genotypes are different between PPD-sensitized individuals and matched controls. METHODS: Genotyping for NAT1 and NAT2 polymorphisms was performed in 147 PPD-sensitized individuals and 200 age- and gender-matched controls. Results Both PPD and monoacetyl-PPD were N-acetylated in vitro by recombinant humanNAT1 and to a lesser extent by NAT2. Genotyping for NAT1*3, NAT1*4, NAT1*10, NAT1*11 and NAT1*14 showed that genotypes containing the rapid acetylator NAT1*10 allele were under-represented in PPD-sensitized cases (adjusted odds ratio 0.72, 95% confidence interval 0.45-1.16). For NAT2, NAT2*4, NAT2*5AB, NAT2*5C, NAT2*6A and NAT2*7B alleles were genotyped. Individuals homozygous for the rapid acetylator allele NAT2*4 were under-represented in cases compared with controls (4.3% vs. 9.4%), but this trend was not significant. CONCLUSIONS: With respect to data indicating that NAT1 but not NAT2 is present in human skin, we conclude that NAT1 genotypes containing the rapid acetylator NAT1*10 allele are potentially associated with reduced susceptibility to PPD sensitization.
Authors: M Peiser; T Tralau; J Heidler; A M Api; J H E Arts; D A Basketter; J English; T L Diepgen; R C Fuhlbrigge; A A Gaspari; J D Johansen; A T Karlberg; I Kimber; J P Lepoittevin; M Liebsch; H I Maibach; S F Martin; H F Merk; T Platzek; T Rustemeyer; A Schnuch; R J Vandebriel; I R White; A Luch Journal: Cell Mol Life Sci Date: 2011-10-14 Impact factor: 9.261
Authors: Marie L A Schuttelaar; Cynthia C A van Amerongen; Jutta Lichter; Brunhilde Blömeke Journal: Contact Dermatitis Date: 2019-05-07 Impact factor: 6.600