Study of functional variants of the BANK1 gene in rheumatoid arthritis

• Published in: Arthritis and rheumatism Vol. 60; no. 2; pp. 372 - 379
• Main Authors: Orozco, Gisela, Abelson, Anna‐Karin, González‐Gay, Miguel A., Balsa, Alejandro, Pascual‐Salcedo, Dora, García, Antonio, Fernández‐Gutierrez, Benjamín, Petersson, Ingemar, Pons‐Estel, Bernardo, Eimon, Alicia, Paira, Sergio, Scherbarth, Hugo R., Alarcón‐Riquelme, Marta, Martín, Javier
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.02.2009; Wiley
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Alleles; Argentina; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - metabolism; Biological and medical sciences; Clinical Medicine; Cohort Studies; Diseases of the osteoarticular system; Female; Genetic Predisposition to Disease; Genotype; Humans; Inflammatory joint diseases; Klinisk medicin; Linkage Disequilibrium; Male; Medical and Health Sciences; Medical sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mexico; Odds Ratio; Polymorphism, Single Nucleotide; Reumatologi och inflammation; Rheumatology and Autoimmunity; Risk Factors; Spain; Sweden; Mexico; Argentina; Sweden; Spain; Immunopathology; Chronic; Rheumatoid arthritis; Diseases of the osteoarticular system; Rheumatology; Autoimmune disease; Inflammatory joint disease
• ISSN: 0004-3591; 1529-0131; 1529-0131
• DOI: 10.1002/art.24244

Objective To investigate 1 functional (rs17266594) and 2 potentially functional (rs10516487 and rs3733197) BANK1 variants, which were previously identified as systemic lupus erythematosus (SLE) susceptibility markers, to test whether they are associated with rheumatoid arthritis (RA). Methods Four different cohorts were included in the study: 1,080 RA patients and 1,368 healthy controls from Spain, 278 RA patients and 568 healthy controls from Sweden, 288 RA patients and 287 healthy controls from Argentina, and 288 RA patients and 288 healthy controls from Mexico. Samples were genotyped for BANK1 single‐nucleotide polymorphisms (SNPs) using a TaqMan 5′‐allele discrimination assay. Statistical analysis comparing allele and genotype distributions was performed with the chi‐square test. Results We did not find a significant association between RA and the rs10516487 and rs17266594 BANK1 polymorphisms. However, there was an increase in the major alleles among RA patients. Similarly, for rs3733197, there was an increase in the major allele among patients in every cohort. Nevertheless, this skewing reached statistical significance in the Spanish (P = 0.01, odds ratio [OR] 1.17 [95% confidence interval (95% CI) 1.03–1.32]) and Argentinean (P = 0.04, OR 1.31 [95% CI 1.00–1.72]) populations. We found a significant association of rs10516487 (P = 0.005, OR 1.15 [95% CI 1.04–1.28]) and rs3733197 (P = 0.0009, OR 1.17 [95% CI 1.07–1.29]) with RA in the pooled analysis. In a 3‐SNP haplotype analysis, we found that the major TGG haplotype was significantly associated with RA (P = 0.005, OR 1.14 [95% CI 1.04–1.25]). In addition, we found a common CAA haplotype that was protective against RA (P = 0.0004, OR 0.82 [95% CI 0.74–0.92]). Conclusion These results suggest that BANK1 SNPs and haplotypes may contribute to RA susceptibility with a low risk.