Lee Young Ho, Bae Sang-Cheol
Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu, Seoul, 02841, Korea.
The Hospital for Rheumatic Diseases, Hanyang University Medical Center, Seoul, Korea.
Rheumatol Int. 2016 Jun;36(6):837-44. doi: 10.1007/s00296-016-3476-5. Epub 2016 Apr 13.
We aimed to investigate whether the PTPRC rs10919563 A/G and Fc gamma receptor 2A (FCGR2A) R131H polymorphisms can predict the response to anti-TNF therapy in rheumatoid arthritis (RA) patients. We conducted a meta-analysis of studies on the association between the PTPRC rs10919563 A/G or the FCGR2A R131H polymorphism and responsiveness to anti-TNF therapy in RA patients. Eighteen studies (twelve on PTPRC and six on FCGR2A) from eight articles involving 3058 patients were considered in this meta-analysis. The meta-analysis showed a significant association between the PTPRC rs10919563 A allele and response to TNF-α blockers in RA. The OR of the PTPRC A allele was significantly lower in responders (OR = 0.584, 95 % CI = 0.409-0.835, P = 0.003). Meta-analysis revealed no association between the FCGR2A HH + HR genotype and responsiveness to TNF blockers in all study subjects (OR = 0.762, 95 % CI = 0.543-1.068, P = 0.115). However, stratification by TNF inhibitor type showed that the FCGR2A HH + HR genotype was associated with responsiveness to adalimumab (OR = 0.591, 95 % CI = 0.369-0.947, P = 0.029), but not infliximab and etanercept (OR = 0.929, 95 % CI = 0.354-2.440, P = 0.881; OR = 0.804, 95 % CI = 0.293-2.207, P = 0.673). The PTPRC rs10919563 A allele shows a poor response to anti-TNF therapy, and the FCGR2A HH + HR genotype shows a poor response to adalimumab for RA. Genotyping for these polymorphisms may be useful for predicting the response to TNF-α blockers with respect to personalized medicine.
我们旨在研究蛋白酪氨酸磷酸酶受体C(PTPRC)基因rs10919563 A/G多态性和Fcγ受体2A(FCGR2A)R131H多态性是否可预测类风湿关节炎(RA)患者对抗肿瘤坏死因子(TNF)治疗的反应。我们对关于PTPRC基因rs10919563 A/G或FCGR2A基因R131H多态性与RA患者对抗TNF治疗反应之间关联的研究进行了荟萃分析。本荟萃分析纳入了8篇文章中的18项研究(12项关于PTPRC基因,6项关于FCGR2A基因),共涉及3058例患者。荟萃分析显示,PTPRC基因rs10919563 A等位基因与RA患者对TNF-α阻滞剂的反应之间存在显著关联。在有反应者中,PTPRC基因A等位基因的比值比(OR)显著更低(OR = 0.584,95%置信区间[CI] = 0.409 - 0.835,P = 0.003)。荟萃分析显示,在所有研究对象中,FCGR2A基因HH + HR基因型与对TNF阻滞剂的反应之间无关联(OR = 0.762,95% CI = 0.543 - 1.068,P = 0.115)。然而,按TNF抑制剂类型分层显示,FCGR2A基因HH + HR基因型与对阿达木单抗的反应相关(OR = 0.591,95% CI = 0.369 - 0.947,P = 0.029),但与英夫利昔单抗和依那西普无关(OR = 0.929,95% CI = 0.354 - 2.440,P = 0.881;OR = 0.804,95% CI = 0.293 - 2.207,P = 0.673)。PTPRC基因rs10919563 A等位基因显示对抗TNF治疗反应不佳,FCGR2A基因HH + HR基因型显示对RA患者的阿达木单抗反应不佳。对这些多态性进行基因分型可能有助于预测针对个性化医疗的TNF-α阻滞剂反应。