Association of anti-CCP positivity and carriage of TNFRII susceptibility variant with anti-TNF-α response in rheumatoid arthritis.
| Title | Association of anti-CCP positivity and carriage of TNFRII susceptibility variant with anti-TNF-α response in rheumatoid arthritis. |
| Publication Type | Journal Article |
| Year of Publication | 2011 |
| Authors | Vasilopoulos, Y., Bagiatis V., Stamatopoulou D., Zisopoulos D., Alexiou I., Sarafidou T., Settas L., Sakkas L., & Mamouris Z. |
| Journal | Clin Exp Rheumatol |
| Volume | 29 |
| Issue | 4 |
| Pagination | 701-4 |
| Date Published | 2011 Jul-Aug |
| ISSN | 0392-856X |
| Keywords | Aged, Antirheumatic Agents, Arthritis, Rheumatoid, Autoantibodies, Biological Markers, Chi-Square Distribution, Cohort Studies, Enzyme-Linked Immunosorbent Assay, Female, Gene Frequency, Genetic Predisposition to Disease, Greece, Haplotypes, Humans, Male, Middle Aged, Peptides, Cyclic, Phenotype, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Receptors, Tumor Necrosis Factor, Type I, Receptors, Tumor Necrosis Factor, Type II, Rheumatoid Factor, Time Factors, Treatment Outcome, Tumor Necrosis Factor-alpha |
| Abstract | 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. |
| Alternate Journal | Clin. Exp. Rheumatol. |
| PubMed ID | 21813066 |
