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已发表论文
遗传性升高欧米伽 - 3 多不饱和脂肪酸与皮肤病风险之间的关联：一项孟德尔随机化研究
Authors Chen JM , Wang Y, Shi Y
Received 26 February 2025
Accepted for publication 1 August 2025
Published 26 September 2025 Volume 2025:18 Pages 2463—2474
DOI https://doi.org/10.2147/CCID.S524519
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Monica K. Li
Jia Min Chen,1,* Yan Wang,2,* Yan Shi3
1The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Reproductive Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Acupuncture, Hangzhou First People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yan Shi, Email zjshane40@163.com
Background: Omega-3 polyunsaturated fatty acids (PUFAs) are potential targets for the treatment of skin diseases due to their anti-inflammatory and immunomodulatory effects. By leveraging a genetic approach known as Mendelian randomization (MR), we sought to determine the causal impact of PUFAs on the likelihood of developing skin diseases among individuals of European ancestry.
Methods: We integrated GWAS data from the CHARGE consortium and UK Biobank to identify genetic instruments for omega-3 PUFAs and desaturase activity, using two-sample MR to assess their associations with six skin diseases.
Results: Elevated levels of omega-3 fatty acids were found to substantially lower the probability of experiencing atopic dermatitis (0.92, [0.85,0.98]), while increased DPA levels correlated with a substantial increase in the probability of squamous cell carcinoma occurrence (2.25, [1.29,3.92]). Increased DHA levels were also associated with a reduced risk of atopic dermatitis (0.90, [0.84,0.96]) but increased the risk of solar dermatitis (1.38, [1.09,1.73]). In addition, tissue-type specific MR analysis revealed that elevated FADS1 expression in fibroblasts significantly inhibited atopic dermatitis development (β = − 0.181, [− 0.276,-0.0853]), while elevated FADS2 expression in non-sun-exposed skin tissues was associated with a reduced risk of squamous cell carcinoma (β = − 0.562, [− 0.833,-0.029]). Conversely, heightened FADS2 expression was strongly linked to a greater likelihood of developing atopic dermatitis in both sun-exposed and sun-protected skin areas (β = 0.107, [0.0348,0.179]; β = 0.192, [0.114,0.0270], respectively).
Conclusion: This study reveals the causal role of omega-3 PUFAs and FADS expression in specific tissues and blood in skin diseases. These findings underscore the potential of PUFA biosynthesis pathways as therapeutic targets for skin disease interventions.
Keywords: Mendelian randomization, ω 3 polyunsaturated fatty acids, delta-5 desaturase, delta-6 desaturase, atopic dermatitis, squamous cell carcinoma
1The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Reproductive Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Acupuncture, Hangzhou First People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yan Shi, Email zjshane40@163.com
Background: Omega-3 polyunsaturated fatty acids (PUFAs) are potential targets for the treatment of skin diseases due to their anti-inflammatory and immunomodulatory effects. By leveraging a genetic approach known as Mendelian randomization (MR), we sought to determine the causal impact of PUFAs on the likelihood of developing skin diseases among individuals of European ancestry.
Methods: We integrated GWAS data from the CHARGE consortium and UK Biobank to identify genetic instruments for omega-3 PUFAs and desaturase activity, using two-sample MR to assess their associations with six skin diseases.
Results: Elevated levels of omega-3 fatty acids were found to substantially lower the probability of experiencing atopic dermatitis (0.92, [0.85,0.98]), while increased DPA levels correlated with a substantial increase in the probability of squamous cell carcinoma occurrence (2.25, [1.29,3.92]). Increased DHA levels were also associated with a reduced risk of atopic dermatitis (0.90, [0.84,0.96]) but increased the risk of solar dermatitis (1.38, [1.09,1.73]). In addition, tissue-type specific MR analysis revealed that elevated FADS1 expression in fibroblasts significantly inhibited atopic dermatitis development (β = − 0.181, [− 0.276,-0.0853]), while elevated FADS2 expression in non-sun-exposed skin tissues was associated with a reduced risk of squamous cell carcinoma (β = − 0.562, [− 0.833,-0.029]). Conversely, heightened FADS2 expression was strongly linked to a greater likelihood of developing atopic dermatitis in both sun-exposed and sun-protected skin areas (β = 0.107, [0.0348,0.179]; β = 0.192, [0.114,0.0270], respectively).
Conclusion: This study reveals the causal role of omega-3 PUFAs and FADS expression in specific tissues and blood in skin diseases. These findings underscore the potential of PUFA biosynthesis pathways as therapeutic targets for skin disease interventions.
Keywords: Mendelian randomization, ω 3 polyunsaturated fatty acids, delta-5 desaturase, delta-6 desaturase, atopic dermatitis, squamous cell carcinoma