Proinflammatory cytokynes IL-1B and TNFa gene polymorphisms in celiac disease?.

CHERÑAVSKY ALEJANDRA; ; CORREA PAULA;; PERIOLO NATALIA, ; GUILLÉN LAURA; ; VAZQUEZ HORACIO; ; MAURIÑO EDUARDO;; BAI JULIO;

Los Angeles, Estados Unidos

Congreso; Digestive disease Week.; 2006

Digestive disease Week

Background/aim: Celiac Disease (CD) is a well-characterized intestinal disorder with a stronggenetic predisposition in the HLA-DQ region. It is also thought that non-HLA genes aredeterminants of CD susceptibility. Our aim was to establish the influence of TNFA and IL1Bgenes polymorphisms as risk factors for developing CD. Materials and methods: We enrolled114 patients with well-established CD and 122 healthy controls with similar gender distributionand ethnicity. Genomic DNA was extracted from anti-coagulated PBMC by standard methods.Genotyping of single nucleotide polymorphisms (SNP) of TNFA -308(G/A) and -238(G/A), andIL1B -511(C/T) and +3953(C/T) was performed by PCR-RFLP. Hardy-Weinberg (H-W)equilibrium and linkage disequilibrium testing were performed using Arlequin software.Results: IL1B but not TNFA markers met H-W equilibrium genotype proportions. There waslinkage disequilibrium between TNFA and IL1B loci but there were no significant differences inany inferred haplotype in both controls and CD patients. Compared with controls, CD patientshad a significant increased prevalence both of the allele TNFA -308A (OR: 1.47, 95% CI: 1.01-2.13) and the TNFA -308AA homozygosis (OR: 3.28, 95% CI: 1.64-6.53). Furthermore, TNFA -308GA heterozygosis constitutes a protective factor (OR: 0.38, 95% CI 0.21-0.70). While the IL1B -511T allele resulted a protective factor for CD (OR: 0.66, 95%CI: 0.45-0.96), no association was found at IL1B +3953 position. CONCLUSIONS: Our findings show that agene polymorphism at TNFA at position -308 is a genetic marker of CD susceptibility in theArgentinean population. Conversely, our data on the contribution of IL1B -511 suggest aprotective role for the T allele.