Psoriasis is generally thought to has the aspects of a genetic predisposition and environmental insults. Around one-third of patients report a family history and identical twin studies suggest a 70% chance of onset if the other twin has psoriasis. The prevalence rate in the Western countries is 2 to 3%, however, it’s only 0.2 % in Japan. The aldo-keto reductase (AKR) 1C3, a NAD(P)H-dependent oxidoreductase, is reported to induce keratin 10 and reduce loricrin in the human skin. Down-regulation of AKR1C3 induces epidermal hyperplasia with abnormal terminal differentiation resembling pathophysiology of psoriasis lesions. In fact, according to GEO array database, AKR1C3 is down regulated in psoriasis lesion (GSE 13355). In this study, we focused on rs12529, a single nucleotide polymorphism (SNP) in human AKR1C3 gene and reported high probability in Caucasians (40-46%) but rare in Japanese (7-8%). DNA is isolated from whole blood obtained from 232 psoriasis patients. The cohort included 138 patients of psoriasis vulgaris, 75 patients of psoriatic arthritis, and 19 patients of generalized pustular psoriasis. Male to female sex ratio is approximately 2.8:1. As the results of TaqMan SNP genotyping assay, Genotype detail of our cohort was G/G:73%, G/C:25.2%, C/C:1.7%. A proportion of G/C or C/C variant was 2-fold higher than two cohorts of healthy Japanese in NCBI database (G/G:86.6%, G/C:13.3%, C/C:0% [ss69068306], G/G:88.6%, G/C:11.3%, C/C:0% [ss71643788;]). There was no correlation between clinical features including BMI, PASI score, age of onset and AKR1C3 variants. Finally, we investigated a correlation between AKR1C3 and filaggrin/loricrin expression in skin samples obtained from psoriasis patients with each genotype of AKR1C3 by immunohistochemistry supporting a role of AKR1C3 polymorphism in psoriasis pathogenesis. Variant of AKR1C3 genotypes may one of the genetic factors predispose to psoriasis.

Genetic variant of aldo-keto reductase (AKR) 1C3 in Japanese psoriasis patients