PTPRC作为类风湿关节炎患者对肿瘤坏死因子抑制剂反应的遗传生物标志物的复制研究。
Replication of PTPRC as genetic biomarker of response to TNF inhibitors in patients with rheumatoid arthritis.
作者信息
Ferreiro-Iglesias A, Montes A, Perez-Pampin E, Cañete J D, Raya E, Magro-Checa C, Vasilopoulos Y, Sarafidou T, Caliz R, Ferrer M A, Joven B, Carreira P, Balsa A, Pascual-Salcedo D, Blanco F J, Moreno-Ramos M J, Fernández-Nebro A, Ordóñez M C, Alegre-Sancho J J, Narváez J, Navarro-Sarabia F, Moreira V, Valor L, García-Portales R, Marquez A, Martin J, Gómez-Reino J J, Gonzalez A
机构信息
Laboratorio de Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.
Rheumatology Unit, Hospital Clinic, IDIBAPS, Barcelona, Spain.
出版信息
Pharmacogenomics J. 2016 Apr;16(2):137-40. doi: 10.1038/tpj.2015.29. Epub 2015 Apr 21.
Genetic biomarkers could be useful for orienting treatment of patients with rheumatoid arthritis (RA), but none has been convincingly validated yet. Putative biomarkers include 14 single nucleotide polymorphisms that have shown association with response to TNF inhibitors (TNFi) in candidate gene studies and that we assayed here in 755 RA patients. Three of them, in the PTPRC, IL10 and CHUK genes, were significantly associated with response to TNFi. The most significant result was obtained with rs10919563 in PTPRC, which is a confirmed RA susceptibility locus. Its RA risk allele was associated with improved response (B=0.33, P=0.006). This is the second independent replication of this biomarker (P=9.08 × 10(-8) in the combined 3003 RA patients). In this way, PTPRC has become the most replicated genetic biomarker of response to TNFi. In addition, the positive but weaker replication of IL10 and CHUK should stimulate further validation studies.
基因生物标志物可能有助于指导类风湿关节炎（RA）患者的治疗，但目前尚无令人信服的验证。假定的生物标志物包括14个单核苷酸多态性，这些多态性在候选基因研究中显示与对肿瘤坏死因子抑制剂（TNFi）的反应相关，我们在此对755例RA患者进行了检测。其中三个位于PTPRC、IL10和CHUK基因中的多态性与对TNFi的反应显著相关。在PTPRC基因中的rs10919563获得了最显著的结果，它是一个已确认的RA易感位点。其RA风险等位基因与更好的反应相关（B = 0.33，P = 0.006）。这是该生物标志物的第二次独立验证（在3003例合并的RA患者中P = 9.08×10⁻⁸）。通过这种方式，PTPRC已成为对TNFi反应最具重复性的基因生物标志物。此外，IL10和CHUK的阳性但较弱的验证结果应促使进一步的验证研究。
Zotero 插件