Candidate pharmacogenetic signals at CCL2 and ITPA associated with JAK inhibitor response in Taiwanese rheumatoid arthritis
Authors' conclusion
Our data prioritise CCL2 and ITPA as candidate pharmacogenetic signals for JAKi response.
Study context
- Population
- Taiwanese patients with rheumatoid arthritis (RA) treated with tofacitinib, baricitinib, or upadacitinib in the Taiwan Precision Medicine Initiative (TPMI)58 candidate single-nucleotide polymorphisms (SNPs) evaluated
- Participants
- 275 patients
- Exposure
- Effective vs Non-effective janus kinase inhibitors (JAKi) response
- Effectiven = 217
- Non-effectiven = 58reference
- Outcome
- Genetic predictors of JAKi effectiveness (58 candidate SNPs, Taiwan Biobank v2 array)
Methodological detailscandidate single-nucleotide polymorphism analysis, integration of cell-type-specific eQTL (scQTLbase) and single-cell RNA sequencing (scRNA-seq), Persistence-based effectiveness endpoint; secondary EULAR-based outcome assessments were exploratory
- Candidate single-nucleotide polymorphism analysis
- Integration of cell-type-specific eQTL (scQTLbase) and scRNA-seq
- Persistence-based effectiveness endpoint; secondary EULAR-based outcome assessments were exploratory
Main finding
As reported in the abstract
Top nominal candidate SNPs for JAKi response
- CCL2 rs1024611/rs4586 and ITPA rs1127354 were the top nominal candidates
- all p<0.05
Observational data: associations, not effects.
Further findings
| Outcome | P value |
|---|---|
| CCL2 expression by scRNA-seqPredominantly across M0/M1/M2 monocytes | P < 0.001 |
| ITPA expression by scRNA-seqEffective vs Non-effective · most notably in M2 monocytes (p<0.001) | P = 0.018 |
| ITPA expression by scRNA-seqNon-effective vs Effective | p 0.004 |
eQTL associations in scQTLbase (GRCh38)
- rs1024611 associated with higher CCL2 in dendritic cells
- rs1127354 associated with higher ITPA in CD14+ monocytes
Original publication
Candidate pharmacogenetic signals at CCL2 and ITPA associated with JAK inhibitor response in Taiwanese rheumatoid arthritis. Clin Exp Rheumatol. Published 27 September 2025. doi:10.
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