Aldo-keto reductase 1C3, which contributes to skin barrier function, is downregulated by single nucleotide polymorphisms predominantly in females with early-onset psoriasis

Author:

Nojiri Yuka1,Nakamura Motoki1,Magara Tetsuya1,Yamamoto Aya1,Ikumi Kyoko1,Nakamura Reiko1,Nishida Emi2,Haarmann-Stemmann Thomas3,Morita Akimichi1

Affiliation:

1. Nagoya City University Graduate School of Medical Sciences

2. Okazaki City Hospital

3. IUF – Leibniz Research Institute for Environmental Medicine

Abstract

Abstract The principal pathology of psoriasis is impaired skin barrier function, epidermal thickening, and granular layer loss. Exposure to extrinsic factors such as tobacco smoke and air pollutants is associated with the development of psoriasis. Aryl hydrocarbon receptors (AHRs) are activated by extrinsic factors associated with the development of psoriasis and act as transcriptional regulators. Expression of aldo-keto reductase (AKR) 1C3 in the epidermal spinous layer regulates epidermal keratinocyte differentiation via the AHR signaling pathway. We investigated whether single nucleotide polymorphisms (SNPs) in AKR1C3 are associated with the pathogenesis of psoriasis. The proportions of rs12529 G/C, C/C variants and rs12387 A/A, A/G variants were 2-fold higher in Japanese psoriasis patients (n = 231) compared with a Japanese healthy cohort. The SNPs were significantly more common than the majority variants in female patients with disease onset ≤ 22 years of age. Patients with rs12529 G > C and rs12387 A > G SNPs exhibited significantly lower AKR1C3 expression and higher expression of late differentiation markers. In conclusion, AKR1C3 downregulation caused by rs12529 G > C and rs12387 A > G SNPs in the epidermis induces abnormal early differentiation of keratinocytes and skin barrier dysfunction, which may contribute to the genetic pathogenesis of psoriasis in young females.

Publisher

Research Square Platform LLC

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