TT genotype of rs10036748 in TNIP1 shows better response to methotrexate in a Chinese population: a prospective cohort study. (24th April 2019)

• Record Type: Journal Article
• Authors: Yan, K.X.; Zhang, Y.J.; Han, L.; Huang, Q.; Zhang, Z.H.; Fang, X.; Zheng, Z.Z.; Yawalkar, N.; Chang, Y.L.; Zhang, Q.; Jin, L.; Qian, D.F.; Li, X.Y.; Wu, M.S.; Xu, Q.H.; Zhang, X.J.; Xu, J.H.
• Is Part Of: British journal of dermatology. Volume 181:Number 4(2019)
• Page Start: 778
• Page End: 785
• Publication Date: 2019-04-24
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.17704
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: Background: Methotrexate (MTX) is an efficacious treatment for psoriasis; however, its widespread application is limited by its unpredictable efficacy. Objectives: To investigate the association of clinical factors and variants of psoriasis susceptibility genes with clinical responses to MTX in a prospective cohort. Methods: A total of 221 patients with psoriasis were recruited. Patients who achieved Psoriasis Area and Severity Index (PASI) improvement ≥ 75% at week 12 were defined as responders, whereas those with PASI improvement < 50% were defined as nonresponders. In 90 screening patients, genetic variants for 18 single‐nucleotide polymorphisms in 14 susceptibility genes, and HLA‐Cw6 status were initially compared for responders and nonresponders. Statistically significant associations in genetic variants were verified in all 221 patients. Results: Overall, 49% and 45% of patients achieved PASI 75 improvement during screening and verification stages, respectively. Concomitant arthritis with psoriasis and high body mass index (BMI) negatively affect the efficacy of MTX. TT genotype of rs10036748 in TNIP1 was significantly associated with PASI 75 response at week 12 (54% and 37%, P < 0·05). A significantly higher PASI 90 response was observed in patients with TT genotype of rs10036748 (27% vs. 12%, P < 0·01) and TC/TT genotype of rs4112788 in LCE3D (25% vs. 13%, P < 0·05) at week 12 compared with those who had other genotypes. After adjustment for all confounding factors, only BMI ( P < 0·05), arthritis ( P < 0·05) and genotype of rs10036748 ( P < 0·05) were significantly associated with clinical responses to MTX. Conclusions: Patients with psoriasis with TT genotype of rs10036748 in TNIP1, with lower BMI, without arthritis will achieve a better response to MTX. Abstract : What's already known about this topic? Methotrexate is the first‐line treatment for moderate‐to‐severe psoriasis. However, there is significant heterogeneity in individual responses to methotrexate. Patients with psoriasis who are positive for HLA‐Cw6 show improved response to methotrexate treatment. What does this study add? Concomitant psoriasis and high body mass index negatively affect the efficacy of methotrexate. TT genotype of rs10036748 in TNIP1 was significantly associated with better responses to methotrexate. What is the translational message? Patients with psoriasis with TT genotype of rs10036748 in TNIP1 will demonstrate a better response to methotrexate. Treatment with methotrexate can be recommended particularly for those patients with psoriasis who have a low body mass index and do not have arthritis. Linked Comment: Cheng. Br J Dermatol 2019; 181 :660–661 . Plain language summary available online Respond to this article