Lei Hao, Chen Xin, Cheng Baochen, Song Liumei, Luo Ruiting, Wang Shengbang, Kang Tong, Wang Qian, Zheng Yan
Department of Dermatology The First Affiliated Hospital of Xi'an Jiaotong University Xi'an China.
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology The Fourth Military Medical University Xi'an China.
Food Sci Nutr. 2023 Jul 5;11(10):6073-6084. doi: 10.1002/fsn3.3543. eCollection 2023 Oct.
Unsaturated fatty acids have been reported to be associated with the risk of psoriasis. However, the causal relationship between them remains unclear This study aimed to explore the causal relationship between unsaturated FAs and psoriasis. Firstly, we obtained genome-wide association study (GWAS) data for psoriasis from the FINNGEN database (number of cases = 4510, number of controls = 212,242) and different FA levels (number of samples = 114,999) from the IEU OpenGWAS Project. Secondly, the genetic correlation coefficient was calculated using linkage disequilibrium fractional regression. Thirdly, a two-sample Mendelian randomization (MR) analysis was performed using independent instrumental variables ( < 5 × 10) to determine the direction of randomization. Finally, expression quantitative trait loci (eQTL)-related analyses of common single nucleotide polymorphisms (SNPs) were carried out to explore the potential molecular mechanisms of unsaturated FAs affecting psoriasis. We found that an increase in the ratio of monounsaturated fatty acids (MUFAs) to total fatty acids could increase the risk of psoriasis (inverse-variance weighted [IVW], adjusted odds ratio [OR] = 1.175; adjusted 95% confidence interval [CI] = 1.045-1.321; adjusted = .007). However, an increase in the ratio of polyunsaturated fatty acids (PUFAa) to total fatty acids could decrease the risk of psoriasis (IVW, adjusted OR = 0.754; adjusted 95% CI = 0.631-0.901; adjusted = .002). Moreover, an increase in the ratio of PUFAs to MUFAs could decrease the risk of psoriasis (IVW, adjusted OR = 0.823; adjusted 95% CI = 0.715-0.948; adjusted = .007). The heterogeneity of data was eliminated, and pleiotropy was not detected. There was no statistical difference in the MR analysis of other fatty acids indices with psoriasis. Further, no statistically significant evidence was found to verify a causal relationship between psoriasis and fatty acid levels in reverse MR. Functional enrichment analysis showed that these eQTL related to common SNPs were mainly involved in organic ion transport, choline metabolism, and the expression of key metabolic factors mediated by PKA, ChREBP, and PP2A. Our study indicated that the ratio of MUFAs to total fatty acids had a positive causal effect on psoriasis, while the ratio of PUFAs to total fatty acids and the ratio of PUFAs to MUFAs had a negative causal effect on psoriasis. Moreover, PKA-, PP2A-, and ChREBP-mediated activation of metabolic factors may play an important role in this process.
据报道，不饱和脂肪酸与银屑病风险相关。然而，它们之间的因果关系仍不明确。本研究旨在探讨不饱和脂肪酸与银屑病之间的因果关系。首先，我们从芬兰基因数据库（FINNGEN database）获取了银屑病的全基因组关联研究（GWAS）数据（病例数 = 4510，对照数 = 212242），并从IEU OpenGWAS项目获得了不同脂肪酸水平的数据（样本数 = 114999）。其次，使用连锁不平衡分数回归计算遗传相关系数。第三，使用独立工具变量（< 5 × 10）进行两样本孟德尔随机化（MR）分析，以确定随机化方向。最后，对常见单核苷酸多态性（SNP）进行表达定量性状位点（eQTL）相关分析，以探索不饱和脂肪酸影响银屑病的潜在分子机制。我们发现，单不饱和脂肪酸（MUFA）与总脂肪酸的比例增加会增加银屑病风险（逆方差加权[IVW]，调整后的优势比[OR] = 1.175；调整后的95%置信区间[CI] = 1.045 - 1.321；调整后的 = 0.007）。然而，多不饱和脂肪酸（PUFA）与总脂肪酸的比例增加会降低银屑病风险（IVW，调整后的OR = 0.754；调整后的95% CI = 0.631 - 0.901；调整后的 = 0.002）。此外，PUFA与MUFA的比例增加会降低银屑病风险（IVW，调整后的OR = 0.823；调整后的95% CI = 0.715 - 0.948；调整后的 = 0.007）。数据的异质性被消除，未检测到多效性。其他脂肪酸指标与银屑病的MR分析无统计学差异。此外，在反向MR中未发现统计学上显著的证据来证实银屑病与脂肪酸水平之间的因果关系。功能富集分析表明，这些与常见SNP相关的eQTL主要参与有机离子转运、胆碱代谢以及由PKA、ChREBP和PP2A介导的关键代谢因子的表达。我们的研究表明，MUFA与总脂肪酸的比例对银屑病有正向因果效应，而PUFA与总脂肪酸的比例以及PUFA与MUFA的比例对银屑病有负向因果效应。此外，PKA、PP2A和ChREBP介导的代谢因子激活可能在此过程中起重要作用。
