title: Association of BANK1 and cytokine gene polymorphisms with type 1 diabetes in Tunisia.
abstract: Type 1 diabetes (T1D) is an autoimmune disease (AID) with both genetic and environmental components. We aimed to investigate the genetic association of polymorphisms in genes previously linked with other AIDs, namely BANK1, IL15 and IL2/IL21 region. A total of 76 T1D patients and 162 controls from Southern Tunisia were recruited for a case-control association study investigating the relationship between sixteen SNPs of the BANK1, IL15 and IL2/IL21 gene region and T1D. In the BANK1 gene, G allele and GG genotype of rs3733197 were significantly increased in the group of T1D patients compared to controls. In addition, in the IL15 gene, the minor allele A of rs10519613 polymorphism was significantly higher in patients than in controls. No significant association was found for SNPS in IL2/IL21 gene region. The analysis of the haplotype structure revealed the G-C-A-C-T haplotype of the IL15 gene as associated with a reduction in the risk of developing T1D, while A-T-A-C-T haplotype increased the risk of developing the disease. Furthermore, in the IL2/IL21 region, only one haplotype consisting of eight SNPs was markedly associated with T1D susceptibility. Moreover, G-C combination of the BANK1/IL15 was significantly increased in T1D patients, compared to controls. Our results establish BANK1 and IL15 as new T1D genetic susceptibility factors and replicate the association of the 4q27 region with T1D. Our data agree with the effect previously observed for other autoimmune conditions and delineate a shared underlying mechanism.
authors.affiliation: Immunology Department, Habib Bourguiba University Hospital of Sfax, Tunisia. Electronic address: zouidi_ferjeni@yahoo.fr.
authors.forename: Ferjani
authors.initials: F
authors.lastname: Zouidi
authors.affiliation: Immunology Department, Habib Bourguiba University Hospital of Sfax, Tunisia.
authors.forename: Mouna
authors.initials: M
authors.lastname: Stayoussef
authors.affiliation: Immunology Department, Habib Bourguiba University Hospital of Sfax, Tunisia.
authors.forename: Dorra
authors.initials: D
authors.lastname: Bouzid
authors.affiliation: Immunology Department, Habib Bourguiba University Hospital of Sfax, Tunisia.
authors.forename: Hajer
authors.initials: H
authors.lastname: Fourati
authors.affiliation: Immunology Department, Habib Bourguiba University Hospital of Sfax, Tunisia.
authors.forename: Olfa
authors.initials: O
authors.lastname: Abida
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Costa
authors.initials: C
authors.lastname: João
authors.affiliation: Immunology Department, Habib Bourguiba University Hospital of Sfax, Tunisia.
authors.forename: Mourad Ben
authors.initials: MB
authors.lastname: Ayed
authors.affiliation: Immunology Department, Habib Bourguiba University Hospital of Sfax, Tunisia.
authors.forename: Raouia
authors.initials: R
authors.lastname: Fakhfakh
authors.affiliation: Pediatric Department, Hedi Chaker University Hospital of Sfax, Tunisia.
authors.forename: Kammoun
authors.initials: K
authors.lastname: Thouraya
authors.affiliation: Pediatric Department, Hedi Chaker University Hospital of Sfax, Tunisia.
authors.forename: Hachicha
authors.initials: H
authors.lastname: Monjia
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Penha-Gonçalves
authors.initials: PG
authors.lastname: Carlos
authors.affiliation: Immunology Department, Habib Bourguiba University Hospital of Sfax, Tunisia.
authors.forename: Hatem
authors.initials: H
authors.lastname: Masmoudi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D016207:Cytokines / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014416:Tunisia
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C447641:BANK1 protein, human; D016207:Cytokines; C569274:IL15 protein, human; D019409:Interleukin-15; D008565:Membrane Proteins
keywords: AID; B-cell scaffold protein with ankyrin repeats 1; BANK1; Cytokine genes; HWE; Hardy–Weinberg equilibrium; LD; OR; RA; SLE; SSc; T1D; Tunisia; Type 1 diabetes; autoimmune disease; linkage disequilibrium; odds ratios; rheumatoid arthritis; systemic lupus erythematosus; systemic sclerosis; type 1 diabetes