Genetic polymorphisms of FOXP3 in Italian patients with systemic sclerosis

• FOXP3 SNPs were tested for association with susceptibility to systemic sclerosis.
• Significant association between rs2280883 and female patients was identified.
• Significant association was found between the SNP and female patients with limited subtype and ACA antibodies.
• FOXP3 rs2280883 may play a protective role in the susceptibility to SSc in females.

A case control study to evaluate the possible influence of FOXP3 polymorphisms (rs3761548 and rs2280883) in the susceptibility of systemic sclerosis in an Italian Caucasian population. Subgroup analysis was also performed to test association between these SNPs and specific disease phenotypes. The study groups consisted of 467 individuals: 228 patients (194 with limited cutaneous form and 34 with diffuse cutaneous form of the disease) and 239 healthy control subjects. Genotyping was performed by high resolution melting analysis. Genotype distribution and allele frequency of the FOXP3 polymorphisms were analyzed statistically, using χ2 or Fisher exact test.Single-marker analysis of allelic and genotype frequencies revealed that SNP rs3761548 was not associated with systemic sclerosis susceptibility.Analysis of genotype and allele distributions of the rs2280883 genetic variant was associated, only in female subjects with systemic sclerosis, its limited subtype, and anti-centromere autoantibodies. Although these findings require replication in a larger set and other populations, FOXP3 rs2280883 may represent a novel susceptibility locus for systemic sclerosis in female subjects.