Table 4 Summary of genetic biomarkers of response to MTX and other DMARDs.
Factors | Predictors of response? | Comments |
|---|---|---|
SE | Yes, worse response to MTX | SE-positive patients seem to respond worse to MTX, especially carriers of the HLA-DRB1*04 allele; association with remission controversial; not extendable to other DMARDs |
RFC1 | Likely, better response to MTX | 80G>A: evidence suggests favorable response in variant allele carriers, although some studies did not confirm it; other identified SNPs may have a role and explain discrepancies |
ABCB1 | Uncertain | 3435C>T: several studies suggesting association with better response, not confirmed in others |
ABCC1-4/ABCG2 | Unknown | Not thoroughly studied |
GGH | Uncertain | Conflicting results regarding SNPs 401C>T, 452C>T and 16T>C |
FPGS | Uncertain | Few studies; contradicting findings with SNP 14G>A, no association of 14G>A with response in two studies |
TYMS | Uncertain | TSER *R/*R: opposite results suggesting better responses for both 2R/2R and 3R/3R and others showing no effect |
| Â | Â | 6 bp-del: favorable role suggested, but not found in other studies |
DHFR | Uncertain | Several SNPs described but addressed in single studies; 317A>G was the only one associated with response but only when using rDAS28 and with marginal effect |
ATIC | Uncertain | 347C>G is the most studied, but conflicting results did not allow a definition of its role; other SNPs have been identified and associated with response in a few studies but lack replication |
MTHFR | No | 677C>T and 1298A>C have been extensively studied and two large meta-analysis found no association with MTX effectiveness |
Polygenic combinations | Uncertain, but promising | Several reports of SNPs combinations associated with response, but lacking replication |