{"title":"基因升高的Omega-3多不饱和脂肪酸与皮肤病风险之间的关系:孟德尔随机研究","authors":"Jia Min Chen, Yan Wang, Yan Shi","doi":"10.2147/CCID.S524519","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong> 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.</p>","PeriodicalId":10447,"journal":{"name":"Clinical, Cosmetic and Investigational Dermatology","volume":"18 ","pages":"2463-2474"},"PeriodicalIF":2.2000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484113/pdf/","citationCount":"0","resultStr":"{\"title\":\"Association Between Genetically Elevated Omega-3 Polyunsaturated Fatty Acids and Skin Disease Risk: A Mendelian Randomization Study.\",\"authors\":\"Jia Min Chen, Yan Wang, Yan Shi\",\"doi\":\"10.2147/CCID.S524519\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong> 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.</p>\",\"PeriodicalId\":10447,\"journal\":{\"name\":\"Clinical, Cosmetic and Investigational Dermatology\",\"volume\":\"18 \",\"pages\":\"2463-2474\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-09-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484113/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical, Cosmetic and Investigational Dermatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/CCID.S524519\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical, Cosmetic and Investigational Dermatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/CCID.S524519","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"DERMATOLOGY","Score":null,"Total":0}
Association Between Genetically Elevated Omega-3 Polyunsaturated Fatty Acids and Skin Disease Risk: A Mendelian Randomization Study.
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.
期刊介绍:
Clinical, Cosmetic and Investigational Dermatology is an international, peer-reviewed, open access journal that focuses on the latest clinical and experimental research in all aspects of skin disease and cosmetic interventions. Normal and pathological processes in skin development and aging, their modification and treatment, as well as basic research into histology of dermal and dermal structures that provide clinical insights and potential treatment options are key topics for the journal.
Patient satisfaction, preference, quality of life, compliance, persistence and their role in developing new management options to optimize outcomes for target conditions constitute major areas of interest.
The journal is characterized by the rapid reporting of clinical studies, reviews and original research in skin research and skin care.
All areas of dermatology will be covered; contributions will be welcomed from all clinicians and basic science researchers globally.