title: Association of rheumatoid arthritis risk alleles with response to anti-TNF biologics: results from the CORRONA registry and meta-analysis.
abstract: In this study, we investigated whether genetic variants known to be related with susceptibility to rheumatoid arthritis (RA) are also associated with response to therapy with anti-tumor necrosis factor (anti-TNF) biologics; 233 patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) RA registry were studied. Findings were combined with results from an international collaborative study (N = 1,283) in a meta-analysis (N = 1,516). Multivariate models investigating the association between single nucleotide polymorphisms (SNPs) and change in RA disease activity were adjusted for age, gender, concomitant methotrexate, and baseline disease activity. In the CORRONA cohort, nominal associations with disease activity improvement were observed for the rs1980422 SNP of the CD28 gene in multivariate models (coefficient -0.377, p = 0.005) but were not significant after adjustment for multiple comparisons (q = 0.10). In the meta-analysis, the only SNP with nominal associations with change in DAS28 was the rs2812378 SNP of the CCL21 gene (coefficient 1.9195, p = 0.0068). This association was not significant after adjustment for multiple comparisons (q = 0.143). We conclude that the established RA risk alleles studied were not significantly associated with response to anti-TNF biologics in the CORRONA cohort or the meta-analysis.
authors.affiliation: Division of Rheumatology, Department of Medicine, New York Presbyterian Hospital, College of Physicians and Surgeons, Columbia University, P&S Building, Suite 10-455, New York, NY 10032, USA. dp2544@columbia.edu
authors.forename: Dimitrios A
authors.initials: DA
authors.lastname: Pappas
authors.forename: Cheongeun
authors.initials: C
authors.lastname: Oh
authors.forename: Robert M
authors.initials: RM
authors.lastname: Plenge
authors.forename: Joel M
authors.initials: JM
authors.lastname: Kremer
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Greenberg
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D018106:CD28 Antigens / Q000235:genetics; D054421:Chemokine CCL21 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; C515478:CCL21 protein, human; D018106:CD28 Antigens; D054421:Chemokine CCL21; D014409:Tumor Necrosis Factor-alpha