The Association of MTHFR C677T and A1298C Polymorphisms with Methotrexate Response and Toxicity in Psoriasis

Background : Methotrexate (MTX) is used to treat psoriasis with various side effects and responsiveness. No predictive indicator of responsiveness or toxicity is available. Objective : To study the association of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase ( MTHFR) gene with the responsiveness and side effects of MTX in psoriatic Thai patients. Methods : The polymorphisms were identified from 86 MTX-treated patients in three hospitals located in southern Thailand using allele-specific PCR. The patients were monitored for the effectiveness and toxicity of the MTX. Results : The C677T genotype frequencies for C/C, C/T, and T/T were 70.9, 26.8, and 2.3%, respectively, and those of the A1298C genotypes for A/A, A/C, and C/C were 57, 32.5, and 10.5%, respectively. Seventy-three patients (87.9%) responded to MTX. The non-responders had higher combined frequencies of C/T and T/T of the C677T (50%) than the responders (24.7%) with no statistical significance ( p = 0.131), but had a lower frequency of CC genotype of the A1298C, although not statistically different ( p =0.691). Eleven patients (12.8%) suffered toxicity. No association of these polymorphisms and MTX toxicity was found. Conclusion : The study did not show an association between these MTHFR polymorphisms with MTX response and toxicity in these patients.