Objectives: The objective of this study was to investigate the association between genes (HLA-DRB1 and PTPN22) and tobacco smoking, separately as well as combined, and serological markers of rheumatoid arthritis (RA) in a French population of RA.
Methods: 274 RA patients with half of them belonging to RA multicase families, were genotyped for HLA-DRB1 allele and for PTPN22-1858 polymorphism. IgM rheumatoid factor and anti-CCP antibodies were determined by ELISA method. The search for association relied on Chi-square test and odds ratio with 95% confidence interval calculation. The interaction study relied on the departure-from-additivity-based method.
Results: The presence of at least one SE allele was associated with anti-CCP antibodies presence (82.5% versus 68.4%, P=0.02), particularly with HLA-DRB1*0401 allele (28.0% versus 16.4%, P=0.01). Tobacco exposure was associated with anti-CCP antibodies, but only in presence of SE. A tendency toward an interaction was found between tobacco, the presence of at least one HLA-DRB1*0401 allele and anti-CCP antibodies (attributable proportion due to interaction= +0.24 [-0.21 +0.76]). The cumulative dose of cigarettes smoking was correlated with anti-CCP antibodies titers (r=0.19, P=0.04). The presence of both SE and 1858T alleles was associated with a higher, but not significantly different, risk for anti-CCP antibodies presence than for each separately. No association was found between PTPN22-1858T allele and tobacco smoking for autoantibodies positivity.
Conclusion: Our findings suggest an association between SE alleles and tobacco smoking for anti-CCP positivity and a tendency toward an interaction between the HLA-DRB1*0401 allele and smoking for anti-CCP positivity in this sample of RA.
- anti-CCP antibodies
- rheumatoid arthritis
- shared epitope
- tobacco smoking