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Causal effects of lipid-lowering drugs on inflammatory skin diseases: Evidence from drug target Mendelian randomisation.
Zang, Chenyang; Li, Jiaxin; Zhang, Ying; Deng, Wenyu; Mao, Manyun; Zhu, Wu; Chen, Wangqing.
Afiliación
  • Zang C; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
  • Li J; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Furong Laboratory, Central South University, Changsha, China.
  • Zhang Y; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China.
  • Deng W; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
  • Mao M; Xiangya School of Medicine, Central South University, Changsha, China.
  • Zhu W; Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Chen W; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
Exp Dermatol ; 33(9): e15157, 2024 Sep.
Article en En | MEDLINE | ID: mdl-39227185
ABSTRACT
Clinical research has revealed that inflammatory skin diseases are associated with dyslipidaemia. Modulating lipids is also a rising potential treatment option. However, there is heterogeneity in the existing evidence and a lack of large-scale clinical trials. Observational research is prone to bias, making it difficult to determine causality. This study aimed to evaluate the causal association between lipid-lowering drugs and inflammatory skin diseases. A drug target Mendelian randomisation (MR) analysis was conducted. Genetic targets of lipid-lowering drugs, including proprotein convertase subtilis kexin 9 (PCSK9) and 3-hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitor, were screened. Common inflammatory skin diseases, including psoriasis, allergic urticaria, rosacea, atopic dermatitis, systemic sclerosis and seborrhoeic dermatitis, were considered as outcomes. Gene-predicted inhibition of PCSK9 was causally associated with a decreased risk of psoriasis (ORIVW [95%CI] = 0.600 [0.474-0.761], p = 2.48 × 10-5) and atopic dermatitis (ORIVW [95%CI] = 0.781 [0.633-0.964], p = 2.17 × 10-2). Gene-predicted inhibition of HMGCR decreased the risk of seborrhoeic dermatitis (ORIVW [95%CI] = 0.407 [0.168-0.984], p = 4.61 × 10-2) but increased the risk of allergic urticaria (ORIVW [95%CI] = 3.421 [1.374-8.520], p = 8.24 × 10-3) and rosacea (ORIVW [95%CI] = 3.132 [1.260-7.786], p = 1.40 × 10-2). Among all causal associations, only PCSK9 inhibition demonstrated a robust causal effect on psoriasis after a more rigorous Bonferroni test (p < 4.17 × 10-3, which is 0.05/12). Modulating lipids via PCSK9 inhibition may offer potential therapeutic targets for psoriasis and atopic dermatitis. Given the potential cutaneous side effects associated with HMGCR inhibitors, PCSK9 inhibitors could be considered viable alternatives in lipid-lowering medication.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Análisis de la Aleatorización Mendeliana Límite: Humans Idioma: En Revista: Exp Dermatol Asunto de la revista: DERMATOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Dinamarca
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Análisis de la Aleatorización Mendeliana Límite: Humans Idioma: En Revista: Exp Dermatol Asunto de la revista: DERMATOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Dinamarca