Psoriasis is a multifactorial disease associated with both genetic and non-genetic factors. We hypothesized that single nucleotide polymorphisms (SNPs) in aldo-keto reductase (AKR) 1C3, which regulates keratinocyte differentiation and loricrin expression in human epidermis, confer a genetic susceptibility to psoriasis. In 232 psoriasis patients, including 171 males and 61 females, a TaqMan SNP genotyping assay revealed that the rs12529 genotype distribution in our cohort was G/G: 75.0%, G/C: 22.8%, and C/C: 2.2%, and the rs12387 genotype distribution was A/A: 75.0%, A/G: 22.8%, and G/G: 2.2%. Surprisingly, these 2 SNPs were always observed in the same patients. The proportion of patients with both the rs12529 G/C, C/C and rs12387 A/G, A/A variants was 2-fold higher than that in 2 cohorts of healthy Japanese individuals in the NCBI database (rs12529, p=0.0088 [vs. ss69068306], p=0.024 [vs. ss71643788]; rs12387, p=0.037 [vs. ss2827707], p=0.024 [vs. ss66361131] Fisher’s exact test). The number of female patients with disease onset ≦22 years of age having both the rs12529 G/C, C/C and rs12387 A/G, G/G variants was significantly higher than that having the rs12529 G/G and rs12387 A/A variants (p=0.0213, Fisher’s exact test). Immunohistochemical staining of lesional psoriasis skin samples obtained from patients with the rs12529 G/C, C/C and rs12387 A/G, G/G variants revealed significantly lower expression of AKR1C3 in the epidermis compared to patients with the rs12529 G/G and rs12387 A/A variants (p=0.0434, Student’s t test). AKR1C3 downregulation in the epidermis induces abnormal terminal differentiation and skin barrier dysfunction. This may contribute to exposure to environmental factors such as tobacco smoke or environmental pollution, which may increase disease susceptibility of psoriasis in young females.

ESDR066 - Single nucleotide polymorphisms in aldo-keto reductase 1C3 associate with early-onset psoriasis in female patients

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING