Lin Jia-Ying, Ma Liang-Juan, Yuan Jin-Ping, Yu Pei, Bai Bing-Xue
Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Front Nutr. 2023 Feb 23;10:1083455. doi: 10.3389/fnut.2023.1083455. eCollection 2023.
Some evidence suggests abnormalities in fatty acids in patients with atopic dermatitis (AD), and benefits of supplementation with these fatty acids have been reported. However, there is still substantial controversy on the correlation between fatty acids and AD. Therefore, the aim of this study was to determine whether fatty acid levels are causally related to AD using a Mendelian randomization approach.
We evaluated the data about the fatty acids levels and AD with various methods from Genome-Wide Association Study (GWAS). GWAS results were available both from European ancestry. Mendelian randomization methods were used to analysis the casual inference of fatty acids on AD. MR Egger and MR-PRESSO were used to determine pleiotropy and heterogeneity. Further analysis was conducted using instruments associated with the genes to address mechanisms involved. We also used Multivariate MR (MVMR) to show the independent casual inference of omega-3 (n-3) fatty acids on AD.
Mendelian randomization (MR) analysis suggests that n-3 fatty acid levels are associated with a lower risk of AD (n-3 OR: 0.92, 95% confidence interval [CI]: 0.87-0.98; = 0.01). Moreover, docosahexaenoic acids (DHA) levels, which is a kind of long-chain, highly unsaturated omega-3 (n-3) fatty acid, and its higher level was associated with a lower risk of AD (DHA ORIVW: 0.91, 95% CI: 0.84-0.98; = 0.02). We ran multivariable MR analysis while controlling for variables within the other types of fatty acids. The effect estimates agreed with the preliminary MR analysis indicating the effect of n-3 fatty acids levels on AD was robust. MR-egger suggest no significant pleiotropy and heterogeneity on genetic instrumental variants. Outliers-corrected MR analyses after controlling horizontal pleiotropy were still robust. The single-SNP analyses revealed that n-3 fatty acids are likely linked to a decreased risk of AD through cluster, highlighting the significance of the gene in the fatty acids synthesis pathway in the development of AD.
Our studies suggest that n-3 fatty acids may reduce the risk of AD. Risk prediction tools based on n-3 fatty acid levels may be valuable methods for improving AD screening and primary prevention. To reduce the risk of AD, individuals could enhance n-3 fatty acids intake through supplement or diet.
一些证据表明特应性皮炎（AD）患者存在脂肪酸异常，并且已有报道补充这些脂肪酸具有益处。然而，脂肪酸与AD之间的相关性仍存在很大争议。因此，本研究的目的是使用孟德尔随机化方法确定脂肪酸水平与AD是否存在因果关系。
我们使用来自全基因组关联研究（GWAS）的各种方法评估了有关脂肪酸水平和AD的数据。GWAS结果来自欧洲血统人群。采用孟德尔随机化方法分析脂肪酸对AD的因果推断。使用MR Egger和MR-PRESSO确定多效性和异质性。使用与这些基因相关的工具进行进一步分析以探讨其中涉及的机制。我们还使用多变量MR（MVMR）来显示ω-3（n-3）脂肪酸对AD的独立因果推断。
孟德尔随机化（MR）分析表明，n-3脂肪酸水平与较低的AD风险相关（n-3比值比：0.92，95%置信区间[CI]：0.87-0.98；P=0.01）。此外，二十二碳六烯酸（DHA）水平，一种长链、高度不饱和的ω-3（n-3）脂肪酸，其水平较高与较低的AD风险相关（DHA逆方差加权法比值比：0.91，95%CI：0.84-0.98；P=0.02）。我们在控制其他类型脂肪酸中的变量的同时进行了多变量MR分析。效应估计与初步MR分析一致，表明n-3脂肪酸水平对AD的影响是稳健的。MR-egger表明在基因工具变体上没有显著的多效性和异质性。在控制水平多效性后进行的异常值校正MR分析仍然稳健。单核苷酸多态性分析表明，n-3脂肪酸可能通过某簇基因与降低的AD风险相关，突出了该基因在脂肪酸合成途径中对AD发生发展的重要性。
我们的研究表明，n-3脂肪酸可能降低AD风险。基于n-3脂肪酸水平的风险预测工具可能是改善AD筛查和一级预防的有价值方法。为降低AD风险，个体可通过补充剂或饮食增加n-3脂肪酸的摄入量。
