Objective: To investigate the relationship of the polymorphic enhancer HS1,2 central to the 3¡¯ enhancer complex regulatory region (IgH3¡¯ EC) of the Ig heavy chain genes with Systemic sclerosis (SSc) disease and compare it to HLA-DR and DQ associations.
Methods: 116 SSc patients were classified as diffuse (dSSc) or limited SSc (lSSc), and as carriers of anti-topoisomerase I (anti-Scl70) or anti-centromere (ACA) antibodies. Allele and genotype frequencies were assessed in the population as a whole and in the two major subsets, dSSc and lSSc. The concentration of peripheral blood immunoglobulin levels was also determined and analyzed according to the genotypes.
Results: The analysis of genotypes for the four alleles of the HS1,2A enhancer showed an increased frequency of the allele *2 in the SSc cohort highly significant vs controls (57% vs 40%, p<0.0001). Considering the autoantibody pattern, we found that the frequency of the 2/2 genotype was increased in ACA+ patients (42%) and anti-Scl70+ patients (31%) compared to the control group (15%). The differences of allelic frequencies among dSSc vs lSSc or ACA+ vs anti-Scl70+ patients were not significant, although highly significant when comparing each sub-group to the control group. HLA-DRB1*11 and DQB1*03 associated with SSc. No association was seen between HS1,2A enhancer polymorphism and HLA alleles.
Conclusions: These data confirm the hypothesis of an increased risk of having SSc in carriers of the allele *2, suggesting an intriguing function of this polymorphism for the B cell regulation.
- HS1, 2 enhancer element
- Ig regulatory region
- systemic sclerosis