Role of FOXP3 gene polymorphism in the susceptibility to Tunisian endemic Pemphigus Foliaceus

•FOXP3 gene polymorphism is implicated in the susceptibility to Tunisian Pemphigus Foliaceus.•FOXP3 gene distributions are significantly different between endemic and sporadic forms.•FOXP3 gene intervenes mainly in the occurrence and clinical presentation of the endemic form.•Additional argument to the particular genetic background of the Tunisian endemic P F.

ObjectiveForkhead box P3 (FOXP3) is an essential and crucial transcription factor of regulatory T-cells. Genetic polymorphisms in the promoter region of FOXP3 gene may alter the gene expression level and, therefore, contribute to several autoimmune diseases susceptibility. We aimed to investigate the possible role of genetic variants of four SNPs (rs3761547, rs3761548, rs3761549 and rs2294021) and a (GT)n microsatellite located in FOXP3 gene in the susceptibility to Tunisian Pemphigus Foliaceus (PF).MethodA case-control study was conducted on 98 patients with different clinical features of PF and 182 matched healthy controls using PCR-RFLP method.ResultsAccording to the epidemio-demographic features of the disease, patients were classified into two groups: an endemic group (n = 33, mean age = 31 [18-48]) versus a sporadic one (n = 65, mean age = 36 [19-84]). In the whole population, rs3761548, rs3761549 and rs2294021 were associated with the susceptibility to PF. Interestingly, significant differences of gene distributions between the two sub-groups of patients were observed. In the endemic group, all associations observed in the whole population were maintained and reinforced and a new association was revealed with rs3761547; while in the sporadic group, only the association with rs3761549 was conserved. Further, the haplotype analysis showed that the G-A-C-15-C risk haplotype was significantly much more expressed in PF patients and specially in the endemic group. The phenotype-genotype correlation revealed that the rs3761548 > AA genotype was significantly correlated with the severity of the disease including Nickolsky sign, generalized form of the disease and the earliest age onset.ConclusionThese results underline the particular genetic background of the Tunisian endemic PF and suggest the implication of FOXP3 gene in the susceptibility and the clinical course of the disease.