MnSOD polymorphisms in sensitized patients with delayed-type hypersensitivity reactions to the chemical allergen para-phenylene diamine:: A case-control study

被引:26
作者
Brans, R
Dickel, H
Bruckner, T
Coenraads, PJ
Heesen, M
Merka, HF
Blömeke, B
机构
[1] Univ Trier, Dept Ecotoxicol & Toxicol, D-54296 Trier, Germany
[2] Rhein Westfal TH Aachen, Dept Dermatol & Allergol, D-52057 Aachen, Germany
[3] Ruhr Univ Bochum, Dept Dermatol & Allergol, D-44791 Bochum, Germany
[4] Univ Heidelberg Hosp, Dept Social Med Occupat & Environm Dermatol, D-69115 Heidelberg, Germany
[5] Univ Groningen, Med Ctr, Dept Dermatol, NL-9700 RB Groningen, Netherlands
[6] Klinikum Bamberg, Dept Anesthesia, D-96049 Bamberg, Germany
关键词
allergic contact dermatitis; polymorphism; genetics; superoxide dismutase; para-phenylene diamine;
D O I
10.1016/j.tox.2005.04.008
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Dyes such as para-phenylene diamine (PPD) or related para-compounds are very common contact sensitizers in man. The corresponding contact dermatitis in sensitized individuals is a complex and common illness associated with considerable morbidity and social cost. It has been found that oxidative stress from reactive oxygen species (ROS) may play an important role in the pre-immunological phase of allergic contact dermatitis to PPD. Manganese superoxide dismutase (MnSOD) is one of the primary enzymes that directly scavenge potential harmful oxidizing species. A valine (Val) to alanine (Ala) substitution at amino acid -9, occurring in the MnSOD gene, has been associated with various disease risk. The aim of our study was to investigate possible associations of the MnSOD 47 T > C genotype in exon 2 (Ala-9Val) and the 339 T > C genotype in exon 3 (Ile58Thr) with contact sensitization to PPD in humans in a case-control study. The study was performed in 157 unrelated cases and 201 age- and gender-matched controls. The MnSOD genotypes were determined using LightCycler allele discrimination assays. No heterozygous (CT) or homozygous carriers (TT) for the Ile58Thr polymorphism were found. The frequency for the C allele of the Ala-9Val polymorphism was 51% (79/157) in cases and 49% (107/201) in controls. Homozygous CC carriers (Ala/Ala) were 27% (43/157) in cases and 23% (46/201) in controls (odds ratio [OR], 1.3; 95% confidence interval [CI], 0.8-2.1). Stratification into subgroups based on gender and age limited the association to females. Increased risk among homozygous CC carriers (Ala/Ala) was only found in the group of older females (over 45 years, 25% versus 18%; OR, 1.5; 95% CI, 0.7-2.34). These data suggest that the C (Ala) allele of MnSOD modifies contact dermatitis risk among older females, but is not an independent susceptibility factor for contact sensitization to PPD. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
引用
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页码:148 / 154
页数:7
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