Uncovering metabolite–inflammatory protein interactions in gout pathogenesis : A 2-sample bidirectional Mendelian randomization study
4 affiliations
- 1Department of Orthopedics, The Affiliated Yan’an Hospital of Kunming Medical University, Kunming, Yunnan, China
- 2Department of Zoology, Kunming Medical University, Kunming, Yunnan, China
- 3School of Basic Medical Sciences, Mudanjiang Medical University, Mudanjiang, Heilongjiang, China
- 4Department of Orthopedics, Tengchong People’s Hospital, Tengchong, Yunnan, China.
Abstract
Gout is a widespread inflammatory arthritis whose current treatments focus mainly on symptom relief and urate lowering. Recent work suggests that circulating metabolites and inflammatory proteins interact in complex ways to influence disease risk, with fibroblast growth factor 19 (FGF19) standing out as a potential regulatory node linking metabolism and inflammation. We performed bidirectional 2-sample Mendelian randomization using genome-wide association study summary statistics for 1440 serum metabolites and 91 inflammatory proteins, with gout outcomes drawn from FinnGen R12. Mediation analyses were then applied to examine whether FGF19 acts as an intermediary in selected metabolite–gout pathways. Genetically predicted levels of vanillactate and histidine betaine were associated with higher gout risk, whereas sphingomyelin species and taurolithocholate 3-sulfate showed protective effects. Among inflammatory proteins, FGF19, adenosine deaminase and FGF5 appeared protective, while cluster of differentiation 244 increased risk. Bidirectional analyses revealed reciprocal relationships, including a negative causal effect of propionylcarnitine on FGF19. Mediation testing further showed that FGF19 explained 7.88% of the total effect of lipid-related metabolites on gout via glycodeoxycholate 3-sulfate and 9.58% via cis-3,4-methyleneheptanoylglycine. These findings indicate that FGF19 may exert protective effects against gout partly by modulating bile acid and fatty acid metabolism. The results offer genetic evidence for metabolic–immune crosstalk in gout pathogenesis and highlight FGF19-related pathways as possible targets for more precise therapeutic strategies.
Related
- Bidirectional Mendelian randomization analysis reveals the causal relationship between rheumatoid arthritis and acute sinusitis
- Uncovering the Role of Small and Intermediate-Length Non-Coding RNAs in Glioma Pathogenesis and Prognosis
- The Bidirectional Relationship Between Tuberculosis and Type 2 Diabetes Mellitus: Pathogenesis, Treatment Challenges, and Prevention Strategies
- Body Mass Index is Causally Associated with Calcific Tendinitis of the Shoulder: A Bidirectional Mendelian Randomization Study.
- Association of 14 matrix metalloproteinases and 4 tissue inhibitors of metalloproteinases on ankylosing spondylitis : A bidirectional Mendelian randomization study
BibTeX
@article{chen2026uncovering,
title = {{Uncovering metabolite–inflammatory protein interactions in gout pathogenesis : A 2-sample bidirectional Mendelian randomization study}},
author = {Shuai Chen and Yudong Gan and Yan Jin and Feng Wang and Zhongxiong Wu and Zenghui Liu and Zixiao Yan and Cheng Li and Shenglong Duan and Zhongzi Zhang},
journal = {Medicine},
year = {2026},
month = oct,
doi = {10.1097/md.0000000000051276},
url = {https://europepmc.org/article/PMC/PMC13727226},
note = {CC BY},
}
RIS
TY - JOUR
TI - Uncovering metabolite–inflammatory protein interactions in gout pathogenesis : A 2-sample bidirectional Mendelian randomization study
AU - Shuai Chen
AU - Yudong Gan
AU - Yan Jin
AU - Feng Wang
AU - Zhongxiong Wu
AU - Zenghui Liu
AU - Zixiao Yan
AU - Cheng Li
AU - Shenglong Duan
AU - Zhongzi Zhang
PY - 2026
DA - 2026/10/30
JO - Medicine
DO - 10.1097/md.0000000000051276
UR - https://europepmc.org/article/PMC/PMC13727226
AB - Gout is a widespread inflammatory arthritis whose current treatments focus mainly on symptom relief and urate lowering. Recent work suggests that circulating metabolites and inflammatory proteins interact in complex ways to influence disease risk, with fibroblast growth factor 19 (FGF19) standing out as a potential regulatory node linking metabolism and inflammation. We performed bidirectional 2-sample Mendelian randomization using genome-wide association study summary statistics for 1440 serum metabolites and 91 inflammatory proteins, with gout outcomes drawn from FinnGen R12. Mediation analyses were then applied to examine whether FGF19 acts as an intermediary in selected metabolite–gout pathways. Genetically predicted levels of vanillactate and histidine betaine were associated with higher gout risk, whereas sphingomyelin species and taurolithocholate 3-sulfate showed protective effects. Among inflammatory proteins, FGF19, adenosine deaminase and FGF5 appeared protective, while cluster of differentiation 244 increased risk. Bidirectional analyses revealed reciprocal relationships, including a negative causal effect of propionylcarnitine on FGF19. Mediation testing further showed that FGF19 explained 7.88% of the total effect of lipid-related metabolites on gout via glycodeoxycholate 3-sulfate and 9.58% via cis-3,4-methyleneheptanoylglycine. These findings indicate that FGF19 may exert protective effects against gout partly by modulating bile acid and fatty acid metabolism. The results offer genetic evidence for metabolic–immune crosstalk in gout pathogenesis and highlight FGF19-related pathways as possible targets for more precise therapeutic strategies.
SN - 0304-5412
SN - 1536-5964
SN - 0025-7974
ER -