Genetic markers for prognosis of antifolate treatment efficacy
View Patent ↗Methods and kits for predicting the efficacy of antifolate (e.g., methotrexate) treatment of rheumatoid arthritis by detecting polymorphisms, particularly single nucleotide polymorphisms, in adenosine pathway genes.
1. A method for determining clinical responsiveness to methotrexate therapy in a human subject afflicted with, or at risk of developing, rheumatoid arthritis comprising detecting in a nucleic acid sample from the subject the presence of a 94A>C polymorphism in the inosine triphosphate pyrophosphatase (ITPA) gene, wherein the presence of said polymorphism is indicative of clinical responsiveness to said methotrexate therapy.
2. The method according to claim 1 , wherein said methotrexate responsiveness is measured as a disease activity score (DAS) less than or equal to 2.4.
3. The method according to claim 1 , wherein the polymorphism is detected by microarray analysis, DNA sequencing or allele specific PCR techniques.
4. The method of claim 1 , further comprising selecting or adjusting said methotrexate therapy depending upon the results of said detecting.
5. The method of claim 4 , wherein said selected or adjusted methotrexate therapy is methotrexate monotherapy, methotrexate combination therapy, or methotrexate biologic therapy.
6. The method of claim 1 further comprising detecting the presence of at least one polymorphism selected from the group consisting of a 34C>T polymorphism in the adenosine monophosphate deaminase (AMPD1) gene, a 2756A>G polymorphism in the methionine synthase (MTR) gene, and a 66A>G polymorphism in the methionine synthase reductase (MTRR) gene, wherein the presence of said polymorphisms is indicative of clinical responsiveness to said antifolate therapy.