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Having in mind the relationships among oxidative stress, psoriasis and common disorders, the association between polymorphisms in the gene encoding the receptor for advanced glycation end products (RAGE) and plaque psoriasis, including patients with a personal history of diabetes mellitus, cardiovascular disorders, cancer and allergy, was investigated. The allele frequencies and genotype distribution combinations of the four polymorphisms in the RAGE gene (6p21.3, G82S, 1704G/T, 2184A/G and 2245A/G) were compared in a case-control study of 272 subjects (130 patients with plaque psoriasis and 142 healthy control subjects of comparable age and sex distribution). The polymerase chain reaction with subsequent restriction analysis was used for detection of genotype variants. There was a significantly higher frequency of the 2184G allele of the 2184A/G RAGE polymorphism in psoriatic patients than in the control subjects (odds ratio 2.18, 95% CI 1.32-3.59, P=0.001). The 2184G allele occurred more often in psoriatic patients with a negative history of cardiovascular diseases (odds ratio 2.38, 95% CI 1.35-4.18, P=0.001, Pcorr=0.004), in those with a negative history of diabetes mellitus (odds ratio 2.05, 95% CI 0.1.22-3.45, P=0.004, Pcorr=0.012) and in those with a negative history of cancer (odds ratio 1.97, 95% CI 1.17-3.31, P=0.007, Pcorr=0.014) compared with the corresponding control subjects. We conclude that the 2184G allele of the RAGE gene is a significant risk factor for plaque psoriasis. The risk is associated with the non-presence of some common, especially cardiovascular, diseases in psoriatic patients.