Refractory sprue has a different association with TNFa and I genes polymorphisms than celiac disease?.

CHERÑAVSKY ALEJANDRA; CORREA PAULA; PERIOLO NATALIA; GUILLÉN LAURA; VAZQUEZ HORACIO; MAURIÑO EDUARDO; BAI JULIO ; ANAYA JUAN MANUEL

Los Angeles, Estados Unidos

Congreso; Digestive disease Week; 2006

Digestive disease Week

Background/aim: Refractory sprue (RS) is a rare and severe celiac-like enteropathy notresponding to a strict gluten-free diet. Polymorphisms at TNFA -308 and IL1B -511 areinvolved in CD susceptibility. Our aim in this study was to analyze the association ofTNFA and IL1B gene polymorphisms in HLA DQ2/DQ8 RS patients.Methods: We enrolled a cohort of 23 consecutive patients diagnosed with RS. We alsostudied a series of patients with CD (n=114) and non-CD controls (C) (n=122). Patientsand controls had a similar Latin-American Caucasian ethnicity. Genomic DNA wasextracted from anti-coagulated PBMC by standard methods and genotyping of singlenucleotide polymorphisms (SNP) at positions TNFA -308(G/A) and -238(G/A), andIL1B - 511(C/T) and +3953(C/T) was performed by PCR-RFLP. Hardy-Weinberg (HW)equilibrium and linkage disequilibrium testing were performed using Arlequinsoftware.Results: Alleles at the individual loci of TNFA and IL1B met H-W equilibriumgenotype proportions in RS but only IL1B individual alleles were in H-W equilibriumin both control populations. TNFA and IL1B loci were linked in control populations butnot in RS. However, no significant differences in inferred haplotypes were found in anypopulation. Polymorphisms at TNFA -308 were not associated with RS but, alleleTNFA -238G and TNF -238GG homozygosis were risk factors (OR: 3.7, 95%CI: 1.5-9.2 and OR:10.0, 95%CI:3.4-29.4, respectively). Furthermore, TNFA -238GAheterozygosis was a protective factor for RS in comparison with C (OR: 0.12, 95% CI:0.04-0.35) and EC (OR: 0.11, 95% CI: 0.04-0.33). No association with RS was found atIL1B locus.CONCLUSIONS: Polymorphisms at proinflammatory cytokine genesdifferentiate RS from CD patients. Polymorphisms at TNFA -238, but not at IL1B, areinvolved in RS susceptibility. Our data on the contribution of TNF -238 polymorphismsare the first evidence for a non-HLA genetic association with the highly severe RS.