title: Role of FOXP3 gene polymorphism in the susceptibility to Tunisian endemic Pemphigus Foliaceus.
abstract: Forkhead 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)nmicrosatellite located in FOXP3 gene in the susceptibility to Tunisian Pemphigus Foliaceus (PF).
  
  
  
  A case-control study was conducted on 98 patients with different clinical features of PF and 182 matched healthy controls using PCR-RFLP method.
  
  
  
  According 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.
  
  
  
  These 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.
authors.affiliation: Immunology Department, Habib Bourguiba Hospital, University of Sfax, Sfax, Tunisia. Electronic address: mariem.benjmea@yahoo.fr.
authors.forename: Mariem
authors.initials: M
authors.lastname: Ben Jmaa
authors.affiliation: Immunology Department, Habib Bourguiba Hospital, University of Sfax, Sfax, Tunisia. Electronic address: olfaabida@yahoo.fr.
authors.forename: Olfa
authors.initials: O
authors.lastname: Abida
authors.affiliation: Dermatology Department, Hedi Chaker Hospital, University of Sfax, Sfax, Tunisia. Electronic address: emnabahloul86@yahoo.fr.
authors.forename: Emna
authors.initials: E
authors.lastname: Bahloul
authors.affiliation: Immunology Department, Habib Bourguiba Hospital, University of Sfax, Sfax, Tunisia; Emirates College of Technology, Abu Dhabi, United Arab Emirates. Electronic address: at_toumi@yahoo.fr.
authors.forename: Amina
authors.initials: A
authors.lastname: Toumi
authors.affiliation: Immunology Department, Habib Bourguiba Hospital, University of Sfax, Sfax, Tunisia. Electronic address: khlif_sana@yahoo.fr.
authors.forename: Sana
authors.initials: S
authors.lastname: Khlif
authors.affiliation: Immunology Department, Habib Bourguiba Hospital, University of Sfax, Sfax, Tunisia. Electronic address: raouiafakh2@yahoo.fr.
authors.forename: Raouia
authors.initials: R
authors.lastname: Fakhfakh
authors.affiliation: Immunology Department, Habib Bourguiba Hospital, University of Sfax, Sfax, Tunisia. Electronic address: elloumi_nesrine@hotmail.fr.
authors.forename: Nesrine
authors.initials: N
authors.lastname: Elloumi
authors.affiliation: Dermatology Department, Hedi Chaker Hospital, University of Sfax, Sfax, Tunisia. Electronic address: khadija@sellami.com.
authors.forename: Khadija
authors.initials: K
authors.lastname: Sellami
authors.affiliation: Dermatology Department, Hedi Chaker Hospital, University of Sfax, Sfax, Tunisia. Electronic address: masmoudiabd@yahoo.fr.
authors.forename: Abderrahmen
authors.initials: A
authors.lastname: Masmoudi
authors.affiliation: Dermatology Department, Hedi Chaker Hospital, University of Sfax, Sfax, Tunisia. Electronic address: Hamida.turki@ms.tn.
authors.forename: Hamida
authors.initials: H
authors.lastname: Turki
authors.affiliation: Immunology Department, Habib Bourguiba Hospital, University of Sfax, Sfax, Tunisia. Electronic address: hatem.masmoudi@yahoo.com.
authors.forename: Hatem
authors.initials: H
authors.lastname: Masmoudi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010392:Pemphigus / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014416:Tunisia; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: Autoimmunity; FOXP3; Immunogenetics; Pemphigus foliaceus; Polymorphism; Regulatory T cells