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Recent genetic research suggests that specific plasma proteins may contribute to ankylosing spondylitis (AS) development. This study sought to explore new therapeutic targets and biomarkers for AS through plasma protein screening.
Eight plasma proteins were linked to ankylosing spondylitis risk, with IL7R, IL12B, CCL8, IL18R1, IL23R, and ERAP1 increasing risk, while TYMP and TNFAIP6 decreased it. IL23R, IL7R, and TYMP emerged as potential therapeutic targets.
Recent genetic research suggests that specific plasma proteins may contribute to ankylosing spondylitis (AS) development. This study sought to explore new therapeutic targets and biomarkers for AS through plasma protein screening.
The study utilized plasma protein data from the latest publications, incorporating 5 genome-wide association studies (GWAS) datasets, including 738 cis-acting protein quantitative trait loci (cis-pQTLs) for about 734 plasma proteins. AS-related GWAS data came from IGAS and European cohorts. Mendelian randomization (MR) analyses with "TwoSampleMR" were executed to evaluate causal links between plasma proteins and AS.
Colocalization assessment identified shared genetic variants. Protein-protein interaction (PPI) network analyses and sensitivity analyses were executed for validating results and exploring treatment targets. A Phenome-wide association study (PheWAS) examined potential side effects of drug-targeted proteins in AS cure.
Overall, 8 plasma proteins were identified: ERAP1, IL23R, IL18R1, TNFAIP6, CCL8, IL12B, TYMP, and IL7R. High levels of ERAP1, IL23R, IL18R1, CCL8, IL12B, and IL7R escalated AS risk, while high TNFAIP6 and TYMP levels reduced it. Colocalization analysis suggested IL23R, IL7R, and TYMP share genetic variants with AS. PPI network analysis highlighted IL23R and IL7R as promising novel treatment targets.
Overall, 8 plasma proteins linked to AS risk were identified, with IL23R, IL7R, and TYMP emerging as key candidates for future therapeutic strategies. More research is warranted to delve into their roles and possibilities for drug repositioning.
Frontiers in Immunology
Investigating potential novel therapeutic targets and biomarkers for ankylosing spondylitis using plasma protein screening
Wenkang You et al.
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