We evaluated the pharmacogenetic influence of genetic polymorphisms in folate pathway genes in Indian rheumatoid arthritis patients receiving methotrexate (MTX).
Twelve polymorphisms within nine folate pathway genes were analyzed for association with MTX response in 322 Indian rheumatoid arthritis (RA) patients and MTX pharmacokinetics in 94 RA patients.
Polymorphisms in GGH, SHMT1 and TS were associated with MTX-related adverse events while SNPs in MTHFR and RFC1/SLC19A1 were associated with MTX efficacy. TS5'UTR and SHMT1 polymorphisms were associated with higher plasma levels of MTX.
Polymorphisms in folate-MTX pathway genes contribute to MTX response and affect MTX concentrations in Indian RA patients. A toxicogenetic index could identify patients who develop adverse events to MTX.