The impacts of gene polymorphisms on methotrexate in Chinese psoriatic patients

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 no...

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Bibliographic Details
Published in:Journal of the European Academy of Dermatology and Venereology 2020-09, Vol.34 (9), p.2059-2065
Main Authors: Chen, M., Chen, W., Liu, P., Yan, K., Lv, C., Zhang, M., Lu, Y., Qin, Q., Kuang, Y., Zhu, W., Chen, X.
Format: Article
Language:English
Subjects:
Adult
Aged
Arthritis, Psoriatic - drug therapy
Arthritis, Psoriatic - genetics
Asian Continental Ancestry Group - genetics
China
Female
Humans
Male
Methotrexate - therapeutic use
Middle Aged
Psoriasis - drug therapy
Psoriasis - genetics
Treatment Outcome
Young Adult
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Summary: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.
ISSN:0926-9959
1468-3083
DOI:10.1111/jdv.16440