MnSOD polymorphisms in sensitized patients with delayed-type hypersensitivity reactions to the chemical allergen...

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.