Genetically Predicted Higher Levels of Caffeic Acid Are Protective Against Ulcerative Colitis: A Comprehensive Metabolome Analysis.
Background It is crucial to pinpoint the metabolites that cause Crohn's disease (CD) and ulcerative colitis (UC) to comprehend their pathogenesis and identify possible targets for therapy. To achieve this goal, we performed the first metabolome-wide Mendelian randomization (MR) study of Japanese pat...
| Publicado en: | Inflammatory Bowel Diseases Vol. 30; no. 12; pp. 2440 - 2449 |
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| Autores principales: | , , , , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Oxford University Press / USA
Dec2024
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=181987481&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 181987481 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 10780998 N0V jtl: Inflammatory Bowel Diseases issn: 10780998 maglogo: N pubinfo: dt: Dec2024 vid: 30 iid: 12 pid: 622 pub: Oxford University Press / USA artinfo: ui: 181987481 181987481 181987481 10.1093/ibd/izae143 181987481 ppf: 2440 ppct: 9 formats: tig: atl: Genetically Predicted Higher Levels of Caffeic Acid Are Protective Against Ulcerative Colitis: A Comprehensive Metabolome Analysis. aug: au: Naito, Takeo Osaka, Ryuya Kakuta, Yoichi Kawai, Yosuke Khor, Seik-Soon Umeno, Junji Tokunaga, Katsushi Consortium, NCBN Controls WGS Nagai, Hiroshi Shimoyama, Yusuke Moroi, Rintaro Shiga, Hisashi Nagasaki, Masao Kinouchi, Yoshitaka Masamune, Atsushi affil: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan sug: subj: Acids, Carbocyclic Therapeutic Use Colitis, Ulcerative Drug Therapy Crohn Disease Drug Therapy Metabolomics Mendelian Randomization Human Japan Metabolites Japanese Persons Descriptive Statistics Odds Ratio Tryptophan Therapeutic Use Colitis, Ulcerative Risk Factors Crohn Disease Risk Factors Causal Attribution Funding Source ab: Background It is crucial to pinpoint the metabolites that cause Crohn's disease (CD) and ulcerative colitis (UC) to comprehend their pathogenesis and identify possible targets for therapy. To achieve this goal, we performed the first metabolome-wide Mendelian randomization (MR) study of Japanese patients with CD and UC. Methods As exposure datasets, genetic instruments with blood-circulating metabolites were obtained from the Tohoku Medical Megabank Organization, which includes 204 metabolites from the genome-wide association study data of 7843 Japanese individuals. As outcome datasets, we enrolled Japanese patients with CD (n = 1803), Japanese patients with UC (n = 1992), and healthy controls (n = 2022). The main analysis utilized the inverse variance–weighted method, while stability of the findings was evaluated through sensitivity analyses. Results After single nucleotide polymorphism (SNP) filtering, 169 SNPs for 45 metabolites were available for MR. Genetically predicted elevated circulating trans-glutaconic acid and tryptophan were associated with a lower CD risk (odds ratio [OR], 0.68; P = 5.95 × 10−3; and OR, 0.64; P = 1.90 × 10−2, respectively). Genetically predicted elevated caffeic acid was associated with a lower UC risk (OR, 0.67; P = 4.2 × 10−4), which remained significant after multiple testing correction. We identified a causal link between UC and 3-hydroxybutyrate (OR, 2.21; P = 1.41 × 10−2), trans-glutaconic acid (OR, 0.72; P = 1.77 × 10−2), and 2-hydroxyvaleric acid (OR, 1.31; P = 4.23 × 10−2). There was no evidence of pleiotropy or reverse causal effects for these candidate metabolites. Conclusions In our metabolome-wide MR study, we discovered a notable protective effect of caffeic acid against UC. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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