The rheumatoid arthritis susceptibility polymorphism PTPN22 C1858T is not associated with leflunomide response or toxicity

被引:8
|
作者
Hopkins, A. M. [1 ,2 ]
O'Doherty, C. E. [1 ,2 ]
Foster, D. J. R. [1 ,2 ]
Suppiah, V. [1 ,2 ]
Upton, R. N. [1 ,2 ]
Spargo, L. D. [3 ]
Cleland, L. G. [3 ,4 ]
Proudman, S. M. [3 ,4 ]
Wiese, M. D. [1 ,2 ]
机构
[1] Univ S Australia, Sansom Inst Hlth Res, Adelaide, SA 2312, Australia
[2] Univ S Australia, Sch Pharm & Med Sci, Adelaide, SA 5001, Australia
[3] Univ Adelaide, Dept Rheumatol, Adelaide, SA, Australia
[4] Univ Adelaide, Discipline Med, Adelaide, SA, Australia
关键词
leflunomide; pharmacogenomics; polymorphism; PTPN22; rheumatoid arthritis; SINGLE-NUCLEOTIDE POLYMORPHISM; MODIFYING ANTIRHEUMATIC DRUGS; T-CELLS; DISEASE; METHOTREXATE; GENE; RECOMMENDATIONS; THERAPY; PEPTIDE;
D O I
10.1111/jcpt.12189
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
What is known and objective A common polymorphism (C1858T) in the gene that encodes the protein tyrosine phosphatase non-receptor type 22 (PTPN22) is associated with altered T-cell responses and increased susceptibility to rheumatoid arthritis (RA) and other autoimmune diseases. Teriflunomide, the active metabolite of leflunomide, reduces T-cell responses through inhibition of tyrosine kinase p56LCK. We examined a potential association between PTPN22 genotype and response or toxicity to leflunomide in Caucasian RA patients taking leflunomide in combination with other disease-modifying antirheumatic drugs (DMARDs). Methods Patients enrolled in the Royal Adelaide Hospital RA inception cohort and taking leflunomide were eligible for inclusion. Participants were followed for 12months after leflunomide initiation or until either another DMARD was added or leflunomide was ceased. Clinical response according to change in 28-joint Disease Activity Score (DAS28) and cessation due to toxicity were assessed. Results and discussion A total of 94 participants were included in the study, 75 of whom carried the CC genotype, 18 the CT, whereas one individual carried the TT genotype. Over the first 12months of leflunomide treatment, there was no statistically significant relationship between carrying the T allele and change in DAS28 (-0 center dot 84 vs. -1 center dot 15, P=0 center dot 446) nor with cessation of leflunomide treatment due to side effects (P=0 center dot 433). These results indicate that PTPN22 C1858T genotype has no effect on response or toxicity outcomes in leflunomide-treated RA patients. What is new and conclusion This is the first study to evaluate the biologically plausible hypothesis that PTPN22 genotype might be a predictor of response/toxicity to leflunomide therapy. Despite this, PTPN22 genotype was not associated with leflunomide response or toxicity in patients with RA.
引用
收藏
页码:555 / 560
页数:6
相关论文
共 50 条
  • [41] The Association Between the PTPN22 C1858T Polymorphism and Systemic Sclerosis: A Meta-Analysis
    Lee, Young Ho
    Choi, Sung Jae
    Ji, Jong Dae
    Song, Gwan Gyu
    ARTHRITIS AND RHEUMATISM, 2011, 63 (10): : S581 - S581
  • [42] PTPN22 C1858T and the risk of psoriasis: a meta-analysis
    Yu-Fu Chen
    Jeffrey S. Chang
    Molecular Biology Reports, 2012, 39 : 7861 - 7870
  • [43] The PTPN22*C1858T functional polymorphism is associated with susceptibility to inflammatory polyarthritis but neither this nor other variants spanning the gene is associated with disease outcome
    Naseem, H.
    Thomson, W.
    Silman, A.
    Worthington, J.
    Symmons, D.
    Barton, A.
    ANNALS OF THE RHEUMATIC DISEASES, 2008, 67 (02) : 251 - 255
  • [44] The non-synonymous C1858T substitution in the PTPN22 gene is associated with susceptibility to the severe forms of alopecia areata
    Kemp, E. Helen
    McDonagh, Andrew J. G.
    Wengraf, David A.
    Messenger, Andrew G.
    Gawkrodger, David J.
    Cork, Michael J.
    Tazi-Ahnini, Rachid
    HUMAN IMMUNOLOGY, 2006, 67 (07) : 535 - 539
  • [45] Meta-analysis reveals PTPN22 1858C/T polymorphism confers susceptibility to rheumatoid arthritis in Caucasian but not in Asian population
    Nabi, Gowher
    Akhter, Naseem
    Wahid, Mohd
    Bhatia, Kanchan
    Mandal, Raju Kumar
    Dar, Sajad Ahmad
    Jawed, Arshad
    Haque, Shafiul
    AUTOIMMUNITY, 2016, 49 (03) : 197 - 210
  • [46] The+1858C/T PTPN22 gene polymorphism confers genetic susceptibility to rheumatoid arthritis in Mexican population from the Western Mexico
    Magdalena Torres-Carrillo, Nora
    Ruiz-Noa, Yeniley
    Esther Martinez-Bonilla, Gloria
    Daniel Leyva-Torres, Sergio
    Torres-Carrillo, Norma
    Azucena Palafox-Sanchez, Claudia
    Elena Navarro-Hernandez, Rosa
    Rangel-Villalobos, Hector
    Oregon-Romero, Edith
    Francisco Munoz-Valle, Jose
    IMMUNOLOGY LETTERS, 2012, 147 (1-2) : 41 - 46
  • [47] The PTPN22 1858C/T functional polymorphism is associated with relapsing polychondritis
    Shilling, Heather
    Wei, Shan
    Gumuscu, Suna Onengut
    Concannon, Patrick
    Buckner, Jane
    CLINICAL IMMUNOLOGY, 2008, 127 : S91 - S91
  • [48] PTPN22 C1858T POLYMORPHISM PROTECTS TYPE 1 DIABETES MELLITUS PATIENTS FROM PROTEINURIA
    Barbuti, Serena
    Focosi, Daniele
    Fornaciari, Silvia
    Vistoli, Fabio
    Curcio, Michele
    Mariotti, Maria L.
    Boggi, Ugo
    Marchetti, Piero
    Scatena, Fabrizio
    TISSUE ANTIGENS, 2012, 79 (06): : 586 - 586
  • [49] The 1858 C>T polymorphism at the PTPN22 gene is associated with rate of joint destruction in patients with rheumatoid arthritis (RA)
    Lie, B. A.
    Viken, M. K.
    Odegard, S.
    Gaarder, P. I.
    Van der Heijde, D. M. F. M.
    Landewe, R. B. M.
    Uhlig, T.
    Kvien, T. K.
    ANNALS OF THE RHEUMATIC DISEASES, 2006, 65 : 74 - 75
  • [50] The PTPN22 C1858T (R620W) functional polymorphism in inflammatory bowel disease
    Zaid Y.
    Senhaji N.
    Bakhtaoui F.Z.
    Serrano A.
    Serbati N.
    Karkouri M.
    Badre W.
    Oudghiri M.
    Martin J.
    Nadifi S.
    BMC Research Notes, 11 (1)