Mendelian Randomization Indicates a Causal Role for Omega-3 Fatty Acids in Inflammatory Bowel Disease.
Mendelian Randomization Indicates a Causal Role for Omega-3 Fatty Acids in Inflammatory Bowel Disease.
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DOI：
10.3390/ijms232214380
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发表时间：
2022-11-19
影响因子：
5.6
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中科院分区：
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炎症性肠病（IBD）的特征在于胃肠道系统的慢性炎症。ω-3脂肪酸是多不饱和脂肪酸（PUFA），主要从饮食中获得，并被推测可降低IBD中涉及的炎症反应;然而，这种关联的因果关系尚未确定。使用双样本孟德尔随机化（MR）评估在英国生物库中测量的249种循环代谢物（作为暴露量）与IBD（作为结局）之间的遗传相关性。代谢物测量和IBD的全基因组关联研究汇总水平数据来自大型欧洲血统队列。我们观察到ω3脂肪酸与IBD具有显著的保护性相关性，在三个IBD汇总遗传数据集中复制了多种模式的MR证据。参与ω3脂肪酸与IBD因果关系的工具变量突出了FADS 2中的内含子SNP rs 174564，FADS 2是一种参与α-亚麻酸去饱和的第一步的蛋白质，导致抗炎性EPA和DHA的产生。观察到ω3与ω6脂肪酸的低比例是一个因果风险因素，特别是克罗恩病。ω3脂肪酸补充剂可以提供减轻IBD中涉及的炎症所需的抗炎反应。
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal system. Omega-3 (ω3) fatty acids are polyunsaturated fatty acids (PUFAs) that are largely obtained from diet and have been speculated to decrease the inflammatory response that is involved in IBD; however, the causality of this association has not been established. A two-sample Mendelian randomization (MR) was used to assess genetic associations between 249 circulating metabolites measured in the UK Biobank as exposures and IBD as the outcome. The genome-wide association study summary level data for metabolite measurements and IBD were derived from large European ancestry cohorts. We observed ω3 fatty acids as a significant protective association with IBD, with multiple modes of MR evidence replicated in three IBD summary genetic datasets. The instrumental variables that were involved in the causal association of ω3 fatty acids with IBD highlighted an intronic SNP, rs174564, in FADS2, a protein engaged in the first step of alpha-linolenic acid desaturation leading to anti-inflammatory EPA and thence DHA production. A low ratio of ω3 to ω6 fatty acids was observed to be a causal risk factor, particularly for Crohn’s disease. ω3 fatty acid supplementation may provide anti-inflammatory responses that are required to attenuate inflammation that is involved in IBD.