Polymorphisms in GNMT and DNMT3b are associated with methotrexate treatment outcome in plaque psoriasis

Methotrexate is used as first-line treatment of moderate to severe psoriasis. Despite the marked variability in outcomes, no pharmacogenetic markers are currently for personalised management therapy. In this retrospective study, we investigated effects genetic predisposition on efficacy and toxicity low-dose methotrexate a cohort 137 patients with plaque We genotyped 16 polymorphisms genes enzymes involved folate–methionine pathway transport, analysed their association using classification regression tree analysis logistic regression. The most pronounced effect observed study was GNMT rs10948059, which identified risk factor inadequate leading discontinuation. Patients carrying at least one variant allele had ~7-fold increased failure compared wild-type genotype, shown by (odds ratio [OR], 6.94; p = 0.0004). Another associated insufficient responses DNMT3b rs2424913, where 4-fold genotype (OR, 4.10; 0.005). Using analysis, show that rs2424913 has more role hence suggest an interaction between these two genes. Further, BHMT rs3733890 hepatotoxicity 3.17; 0.022), prominent reason also variants transporters OATP1B1 (rs2306283/rs4149056 SLCO1B1 haplotypes) ABCC2 (rs717620) failure. associations have not been reported previously. These data methionine cycle (which affect cell methylation potential) might significant roles Further studies warranted validate potential identified. • Novel rs10948059 main alleles increases Polymorphisms transporter increase risk. hepatotoxicity.