Are haplotypes in a single methotrexate pathway more predictive for response in rheumatoid arthritis than in different pathways?
Abstrakt
This study found the association of MTX non-response with SNPs in MTHFR (rs1801131, rs1801133), MS (rs1805087), MTRR (rs1801394) and ATIC (rs2372536, rs4673993, rs7563206, rs12995526). Three haplotypes in GGH (CC haplotype for rs3758149 and rs12681874) and ATIC (haplotypes CGTTT and CTTTC for ATIC combination 1 and 2) genes were found to be associated with nonresponse to MTX.
Importantly, these haplotypes have high haplotype frequencies (22.4%, 48.1%, 34.6%, respectively). Therefore, we can hypothesize that the influence of SNPs in the de novo purine synthesis pathway, polyglutamation pathway and in ADORA2A receptor is mutually strengthened, i.e. it leads to phenotypic manifestation with higher clinical significance observed as non-response to MTX treatment.