A gene variant of <scp>AKR1C3</scp> contributes to interindividual susceptibilities to atopic dermatitis triggered by particulate air pollution

Vogeley, Christian; Kress, Sara; Lang, Dieter; Vogel, Christoph F.A.; Hartung, Frederick; Brenden, Heidi; Nakamura, Minoru; Rossi, Andrea; Krutmann, Jean; Schikowski, Tamara; Haarmann‐Stemmann, Thomas

doi:10.1111/all.15622

Cited by 9 publications

(5 citation statements)

References 8 publications

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“…Shiota et al have shown that the H5Q mutation caused by rs12529 has only a minor effect on AKR1C3 activity and protein stability 31 , and similar results were obtained by Detlefsen et al 32 . However, our recent report showed that the G > C mutation in rs12529 (major allele in Europe) resulted in less protein stability compared to the major allele in Asia 33 . On the other hand, the ratio of major allele (A) to minor allele (G) in rs12387 is almost the same worldwide, and A > G mutations are found in approximately 15% of cases.…”

Section: Discussionmentioning

confidence: 92%

Influence of aldo–keto reductase 1C3 polymorphisms in early-onset female psoriasis patients

Nojiri

Nakamura

Magara

et al. 2023

Sci Rep

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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 twofold 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.

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Section: Discussionmentioning

confidence: 92%

Influence of aldo–keto reductase 1C3 polymorphisms in early-onset female psoriasis patients

Nojiri

Nakamura

Magara

et al. 2023

Sci Rep

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“…The deficiency in AKR1D1 is presented by neonatal cholestasis and liver failure in early infancy ( Zhao et al, 2023 ). Genetic variants in the AKR1B10 locus influence human eating behavior ( Rohde et al, 2015 ), AKR1C2 gene variants are linked to adipose tissue distribution ( Ostinelli et al, 2021 ), and certain gene variants of AKR1C3 contribute to interindividual susceptibilities to atopic dermatitis ( Vogeley et al, 2023 ). AKRs are also implicated in resistance to cancer chemotherapeutic agents, either because they are directly involved in their metabolism or because they help eradicate the cellular stress created by these agents ( e.g.…”

Section: Discussionmentioning

confidence: 99%

Phylogenetic and transcriptomic study of aldo-keto reductases in Haemonchus contortus and their inducibility by flubendazole

Štěrbová,

Raisová Stuchlíková,

Rychlá

et al. 2024

International Journal for Parasitology: Drugs and Drug Resistan

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“…This is due to the nature of AhR signaling in skin: patients with AD have dominant non-canonical AhR signaling that is pathologic, so AhR agonists are helpful for restoring the balance between canonical and non-canonical pathways in these patients [29]. The activation of the AhR pathway may also contribute to greater aldo-keto reductase expression, which affects mast cell activation and stimulates a Th2 response [30].…”

Section: Aryl Hydrocarbon Receptor Pathwaymentioning

confidence: 99%

Air Pollution and Atopic Dermatitis, from Molecular Mechanisms to Population-Level Evidence: A Review

Fadadu

Abuabara

Balmes

et al. 2023

IJERPH

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Atopic dermatitis (AD) has increased in prevalence to become the most common inflammatory skin condition globally, and geographic variation and migration studies suggest an important role for environmental triggers. Air pollution, especially due to industrialization and wildfires, may contribute to the development and exacerbation of AD. We provide a comprehensive, multidisciplinary review of existing molecular and epidemiologic studies on the associations of air pollutants and AD symptoms, prevalence, incidence, severity, and clinic visits. Cell and animal studies demonstrated that air pollutants contribute to AD symptoms and disease by activating the aryl hydrocarbon receptor pathway, promoting oxidative stress, initiating a proinflammatory response, and disrupting the skin barrier function. Epidemiologic studies overall report that air pollution is associated with AD among both children and adults, though the results are not consistent among cross-sectional studies. Studies on healthcare use for AD found positive correlations between medical visits for AD and air pollutants. As the air quality worsens in many areas globally, it is important to recognize how this can increase the risk for AD, to be aware of the increased demand for AD-related medical care, and to understand how to counsel patients regarding their skin health. Further research is needed to develop treatments that prevent or mitigate air pollution-related AD symptoms.

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A gene variant of AKR1C3 contributes to interindividual susceptibilities to atopic dermatitis triggered by particulate air pollution

Cited by 9 publications

References 8 publications

Influence of aldo–keto reductase 1C3 polymorphisms in early-onset female psoriasis patients

Influence of aldo–keto reductase 1C3 polymorphisms in early-onset female psoriasis patients

Phylogenetic and transcriptomic study of aldo-keto reductases in Haemonchus contortus and their inducibility by flubendazole

Air Pollution and Atopic Dermatitis, from Molecular Mechanisms to Population-Level Evidence: A Review

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