title: Association of ZAP70 and PTPN6, but Not BANK1 or CLEC2D, with inflammatory bowel disease in the Tunisian population.
abstract: Inflammatory bowel diseases (IBDs), consisting of ulcerative colitis (UC) and Crohn's disease (CD), are complex disorders with multiple genes contributing to disease pathogenesis. We aimed to identify the associations of genetic variations in the ZAP70, PTPN6, BANK1, and CLEC2D genes encoding for intracellular signaling molecules with IBDs. One hundred seven patients (39 CD and 68 UC) with IBD and 162 healthy control subjects from the Southern Tunisia were recruited. We genotyped 4 single-nucleotide polymorphisms (SNPs) in ZAP70 (rs1020396, rs11686881, rs13420683, and rs17695937), 2 SNPs in PTPN6 (rs7310161 and rs759052), 3 SNPs in BANK1 (rs10516487, rs17266594, and rs3733197), and 1 SNP in CLEC2D (rs3764021). ZAP70 displayed a strong genetic association with CD for rs13420683 [allele C, p=0.003, P(corr)=0.006, odds ratio (OR)=2.25 (1.32; 3.85); genotype CC, p=0.016, P(corr)=0.048, OR=2.57 (1.22; 5.41)]. However, in UC, a weak association with PTPN6 was observed [TT (p=0.01; P(corr)=0.03; OR=2.11 (1.18; 3.76)]. No significant association in the BANK1 and CLEC2D genes was observed. These results suggest the involvement of the ZAP70 and PTPN6 genes in the genetic component conferring a general susceptibility to CD and UC, respectively. This work provides motivation for studies aiming to replicate these findings in larger populations.
authors: Immunology Department, Medicine School and Habib Bourguiba Hospital, Sfax, Tunisia. dorra-ing@voila.fr
authors: Dorra
authors: D
authors: Bouzid
authors: Hajer
authors: H
authors: Fourati
authors: Ali
authors: A
authors: Amouri
authors: Isabel
authors: I
authors: Marques
authors: Olfa
authors: O
authors: Abida
authors: Samy
authors: S
authors: Haddouk
authors: Mourad
authors: M
authors: Ben Ayed
authors: Nabil
authors: N
authors: Tahri
authors: Carlos
authors: C
authors: Penha-Gonçalves
authors: Hatem
authors: H
authors: Masmoudi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics*; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology / Q000235:genetics; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D014416:Tunisia / Q000453:epidemiology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C447641:BANK1 protein, human; C400041:CLEC2D protein, human; D037181:Lectins, C-Type; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6