Association study of B-cell marker gene polymorphisms in European Caucasian patients with systemic sclerosis

Background. BANK 1 and BLK B-cell genetic markers have been reproducibly and convincingly found to contribute to susceptibility to systemic sclerosis (SSc). Objectives. To determine whether other B-cell genetic markers including CD 19. CD20 CD22 and CD24 polymorphisms affect susceptibility 10 SSc in the European Caucasian population. Methods. A case-control study was performed in 900 patients with SSc and 1034 healthy controls. Among the whole SSc population, 304 (34%) had the diffuse cutaneous subtype, 551 (61%) had the limited cutaneous subtype. 732 (81%) were positive for antinuclear antibodies, 331 (37%) were positive for amicentromere antibodies and 228 (25%) for the topo-isomerase I. Genotyping has been performed for CD 19 rs35979293, CD 19 rs2904880, CD20 rs7126354, CD20,rs3802954, CD20 rs105146, CD20 rs4939364 CD22 rs10406069, CD22 rs10413500, CD22 rs10419538, CD22 rs34826052 and CD24 ins-del polymorphisms. Results. Genotype frequencies were at the Hardy-Weinberg equilibrium in the control population for all the SNPs investigated and observed frequencies were very similar to those expected in the European population. Allelic and genotypic frequencies for, all these tested SNPs were found to be similar in SSc patients and controls. Moreover, subphenotype analyses in particular for subgroups having the diffuse cutaneous subset or topo-isomerase positive antibodies. which are the most associated with BANK 1 variants, did not detect any difference between SSc patients and controls. Conclusion. These results obtained through a large cohort of European ccutcasian patients with SSc do not support the contribution of CD 19, CD20, CD22, CD24 variants to the genetic susceptibility of SSc.