Study Analyzes Metabolites and AD

Bidirectional two-sample Mendelian randomization (MR) analyses in a study published in Scientific Reports indicated that 22 metabolites and one inflammatory protein (S100A12) were significantly associated with atopic dermatitis (AD) pathogenesis.

“The levels of amino acid metabolites in serum induce the pathogenesis of atopic dermatitis by mediating the inflammatory protein S100A12,” by researchers at Beijing University of Chinese Medicine, aimed to determine the genetic relationship between metabolites and AD and to determine the pathways through which amino acid metabolites affect AD.

S100A12 is a mediator of amino acid metabolites (N6-methyllysine; N2-acetyl,N6,N6-dimethyllysine, and N6,N6-dimethyllysine) that are genetically associated with AD. S100A12 was positively correlated with the infiltration of multiple immune cell types in lesional AD skin.

“The amino acid metabolites N6-methyllysine; N2-acetyl,N6,N6-dimethyllysine, and N6,N6-dimethyllysine influence AD pathogenesis by mediating S100A12 expression,” the researchers wrote.

Using bidirectional two-sample MR, they analyzed the causal relationships between metabolites and AD. The principal MR test of causal effects was conducted using inverse-variance weighted regression, and they used reverse MR analysis to exclude reverse causality. They also performed the MR-PRESSO test to detect and correct for possible pleiotropic effects, and used the Cochran Q test to assess heterogeneity. Two-step MR was utilized to analyze the mediating factors between amino acid metabolites and the onset of AD. The correlation between mediating factors (inflammatory protein S100A12) and immune cell infiltration was analyzed using the edgeR and GSVA software packages. Using single-cell sequencing data from skin tissues of patients with AD, they studied the regulatory role of the S100A12 gene in immune cells. Multiple drug databases and macromolecular docking were used to search for S100A12-targeting drugs.