Combined analysis of polymorphisms of the tumor necrosis factor-alpha and interleukin-10 promoter regions and polymorphic xenobiotic metabolizing enzymes in psoriasis

Environmental and genetic factors are thought to interact in the manifestat ion of psoriasis, but knowledge about the involved genes and antigens is in complete. This study has focused on the association between psoriasis and i nherited variations in xenobiotic metabolism and cytokine production as two components that may influence cutaneous immune responses to foreign substa nces. Polymorphisms of N-acetyltransferase 2, glutathione S-transferases T1 and Mi, and promoter polymorphisms of the genes encoding for tumor necrosi s factor-alpha and interleukin-10 were investigated in 151 Caucasian patien ts with psoriasis (100 with type I and 51 with type II psoriasis) and in 12 3 healthy controls. Polymorphisms were detected by polymerase chain reactio n-based methods, restriction enzyme analysis, and direct sequencing. There were no significant differences in the distribution of enzyme polymorphisms or point mutations at position -1082 of the interleukin-10 promoter betwee n the psoriasis groups and the control group. The G --> A polymorphism at p osition -238 of the tumor necrosis factor-a promoter (TNF alpha-238*A allel e) was more common in type I psoriasis (27%) than in the controls [9.8%; od ds ratio 3.4 (95% confidence interval 1.6-7.2); p = 0.0012; p(corr) = 0.018 ], Surprisingly, this overrepresentation of the tumor necrosis factor-alpha - 238*A allele was observed in male patients [4.1 (1.5-11.0); p = 0.0046; p(corr) = 0.064] but not in female patients [1.8 (0.5-6.5); p = 0.5]. The G --> A polymorphism at position -308 of the tumor necrosis factor-alpha pro moter was less frequent in type I psoriasis (23%) compared with controls (3 5.7%), although the negative association was weak [0.54 (0.3-0.97); p = 0.0 41; p(corr) = not significant]. The distribution of the TNF alpha 238*A and TNF alpha-238*A alleles was similar in type II patients and controls. Our results suggest that male carriers of the G --> A polymorphism at position -238 of the tumor necrosis factor-alpha promoter are at an increased risk t o develop early-onset psoriasis.