Association of anti-CCP positivity and carriage of TNFRII susceptibility variant with anti-TNFα response in rheumatoid arthritis

Clinical and Experimental Rheumatology

Loukas Settas¹  Yiannis Vasilopoulos¹  Ioannis Alexiou¹  Zissis Mamouris¹  Vasilis Bagiatis¹  Theologia Sarafidou¹  Dimitris Zisopoulos¹  Dimitra Stamatopoulou¹  Lazaros Sakkas¹ 

关键词: Pharmacogenetics;    anti-TNF;    association;    anti-CCP;    polymorphism;    Anti-TNF;    pharmacogenetics;    association;    anti-CCP;    polymorphism;   

DOI  :  

学科分类：医学（综合）

来源: Pacini Editore SpA

【 摘 要 】

OBJECTIVES: To investigate the possible influence of tumour necrosis factor-alpha (TNF), TNF receptor I (TNFRI) and TNF receptor II (TNFRII) gene polymorphisms on anti-TNF treatment responsiveness, stratified by autoantibody status. METHODS: A Greek multi-centre collaboration was established to recruit a cohort of patients (n=100) with active RA treated with anti-TNF drugs. TNF g.-238G>A (rs361525), g.-308G>A (rs1800629), g.-857C>T (rs1799724), TNFRI c.36A>G (rs4149584) and TNFRII c.676T>G (rs1061622) polymorphisms were genotyped by PCRRFLP assays. Serum RF and anti-CCP antibody status were determined using commercially available kits. Single-SNP, haplotype and stratification by autoantibody status analyses were performed in predicting response to treatment by 6 months, defined as the absolute change in DAS28. RESULTS: 31 patients (31%) were defined as non-responders due to failure to fulfill the DAS28 criteria. 79% and 66% were RF and anti-CCP positive, respectively. None of the genotyped SNPs was alone associated with responsiveness to drug treatment. However, after stratification by autoantibody status, carriage of TNFRII c.676G allele was associated with poorer response to drug treatment in anti-CCP positive patients (p=0.03), after 6 months of anti-TNF therapy. CONCLUSIONS: In concordance with previous studies, genetic polymorphisms alone cannot be used to safely predict clinical response to anti-TNF therapy however the combination of genetic factors and autoantibody status warrants further investigation in larger independent cohorts.

【 授权许可】

Unknown