The impacts of gene polymorphisms on methotrexate in Chinese psoriatic patients

Abstract

Background Methotrexate (MTX) is the first‐line treatment for psoriasis in China. The metabolic processes of MTX include various proteins and genes. Previous studies have shown that gene polymorphisms had significant impacts on the efficacy of MTX. However, the influence of gene polymorphisms has not been reported in the Chinese psoriatic patients. Objective The aim of this study was to verify the impacts of candidate genes polymorphisms on the effectiveness of MTX in a Chinese psoriatic population. Methods In this study, we enrolled 259 psoriasis patients from two clinical centres. Each of them received MTX treatment at 7.5–15 mg/week for at least 8 weeks. Patients were stratified as responders and non‐responders according to whether the Psoriasis Area and Severity Index score declined more than 75% (PASI75). According to previous reports, 16 single nucleotide polymorphisms (SNPs) were selected and genotyped for each patient using the Sequenom platform. Fisher’s exact test, the chi‐square test, Mann–Whitney tests and ANOVA analyses were used for statistical analysis. Results Among 259 patients, there were 182 males and 77 females, 63 patients with psoriatic arthritis and 196 patients without arthritis phenotype, and the age of all patients ranged from 19 to 70 years (49.7 ± 13.6). The baseline PASI value of patients was 13.8 ± 8.5, and 33.2% of patients achieved a PASI75 response after MTX treatment. Patients carrying the ATP‐binding cassette subfamily B member 1 gene (ABCB1) rs1045642 TT genotype were associated with more severe psoriasis skin lesion (P = 0.032). Furthermore, the ABCB1 rs1045642 TT genotype was found to be more frequent in non‐responders (P = 0.017), especially in moderate‐to‐severe patients (P = 0.002) and patients without psoriatic arthritis (P = 0.026) after MTX treatment. Conclusion We have demonstrated for the first time that polymorphism of the ABCB1 rs1045642 TT genotype is predictive of a worse clinical response of skin lesions to MTX therapy in a Chinese psoriatic population.

ABCB1 in dermatology: roles in skin diseases and their treatment

“…In dermatology, ABCB1 polymorphism is related to methotrexate responsiveness in psoriasis. In Chinese patients with psoriasis, ABCB1 rs1045642 TT genotype is associated with poor responsiveness to methotrexate, particularly in patients with moderate to severe psoriasis [ 97 ]. Other investigations involving methotrexate and ABCB1 have mainly focused on rheumatoid arthritis and malignancy.…”

Systemic Methotrexate Treatment in 42 Children with Severe Plaque Psoriasis: A Retrospective Study in China

“…Several reasons may explain the variation of therapeutic outcomes. First, personal or racial variations due to polymorphisms in the genetic background of the MTX metabolic pathway may lead to different therapeutic outcomes [18][19][20][21], patients enrolled in our study were Asians, while the majority of patients reported by other studies were Caucasian. Second, different criteria for case selection may lead to different outcomes.…”

The Impact of ANxA6 Gene Polymorphism on the Efficacy of Methotrexate Treatment in Psoriasis Patients

“…A recent study showed that the polymorphisms of rs216195 in SMG6, rs1050301 in IMMT, and rs2285421 in UPK1A could be associated with the clinical response to MTX by the whole exon high-throughput sequencing technology [19]. However, there are likely to be some controversial results in the pharmacogenetic studies due to the small sample size and confounding factors such as environment and ethnicity [19, 20]. Larger-scale and multicenter studies are necessary to provide genetic markers associated with the efficacy into the clinical practice for personalized medicine [21, 22].…”