Study Identifies Causal Link Between Metabolites and Gout

By Cailin Conner - Last Updated: December 8, 2023

A 2-sample Mendelian randomization (MR) analysis that examined the association between metabolites and gout found that 14 metabolites had a causal effect on gout. The study was published in the European Journal of Clinical Investigation.

Advertisement

“Given that the causal impacts of blood metabolites on gout were poorly understood, we used a 2-sample MR analysis based on genome-wide association study (GWAS) statistics to explore the causal relationship between a wide range of these blood metabolites and the risk of gout,” the investigators wrote. The aim was for study outcomes to not only deepen the understanding of the pathophysiological mechanisms of gout but also to establish a reliable foundation for developing practical clinical strategies for the early diagnosis, prevention, and treatment of gout.

The study utilized a large-scale GWAS dataset to establish associations between genetic variants and gout. The potential causal associations between 486 serum metabolites were evaluated. The inverse variance weighting (IVW) method served as the primary tool for generating results, supplemented by sensitivity analyses such as MR-Egger, weighted median, Cochran’s Q test, Egger intercept test, and leave-one-out analysis to enhance result reliability.

The combined application of IVW and sensitivity analyses pinpointed 14 metabolites with a statistically significant causal effect on gout (P<.05). Hexadecanedioate was notably linked to a reduced risk of gout (IVW odds ratio, 0.50; 95% CI, 0.38-0.67) among the 14 identified metabolites, while the others, including 3-methylxanthine, ibuprofen, 2-aminobutyrate, isovalerate, inosine, undecanoate (11:0), 1-linoleoylglycerol (1-monolinolein), bradykinin, des-arg (9), benzoate, pro-hydroxy-pro, gamma-glutamylleucine, 1-methylxanthine, and piperine, reached nominal significance levels.

The study’s metabolic pathway analysis further identified a pathway potentially linked to the development of gout. Specifically, the investigators uncovered a possible metabolic pathway linked to the development of gout, with 1-methylxanthine implicated in Caffeine metabolism (P=.02).

Regarding the implications of their study, the investigators stated, “These metabolites may be helpful in clinical screening and prevention of high-risk groups of gout, as well as candidate molecules for future mechanism exploration.”

Advertisement