Genetic polymorphisms predict psoriasis vulgaris response to methotrexate
Single nucleotide polymorphisms (SNPs) in the SMG6, IMMT and UPK1A genes affect the efficacy of methotrexate in patients with psoriasis vulgaris, a new study has shown.
Whole-exon high-throughput sequencing technology was used to assess the DNA of 22 psoriasis vulgaris patients, half of whom were nonresponders (mean age 44±13 years; 50 percent male; responders: mean age 48±15 years; 50 percent male) to methotrexate. Medication response was defined as a decrease in the Psoriasis Area and Severity Index >75 percent.
Fifty SNPs were selected for further validation by the MassARRAY method. Of these, 36 putative SNPs were identified in the present study, while the remaining 14 had been previously reported in the literature. After selecting for SNPs with a frequency >5 percent, genotyping rate ≥95 percent, and which satisfied the Hardy-Weinberg equilibrium, 42 remained qualified for further analysis.
On multivariate logistic regression analysis, three SNPs achieved statistical significance. The rs216195 GT (odds ratio [OR], 5.574; 95 percent CI, 1.1035–30.032; p=0.046) and GG (OR, 6.174; 1.114–33.922; p=0.037) genotypes of the SMG6 gene were all significantly associated with an effective response relative to the TT genotype.
For the IMMT gene, the rs1050301 AA (OR, 0.246; 0.061–0.0990; p=0.049) genotype was correlated with a poorer response relative to the GG phenotype. The rs2285421 TC (OR, 4.420; 1.175–16.630; p=0.028) and CC (OR, 2.795; 0.689–11.331; p=0.029) genotypes of the UPK1A gene were associated with a better response relative to the TT genotype.