TY - JOUR
T1 - The simultaneous presence of IL-1B and TNFA two-positions risk haplotypes enhances the susceptibility for celiac disease
AU - Cherñavsky, Alejandra Claudia
AU - Páez, María Carolina
AU - Periolo, Natalia
AU - Correa, Paula
AU - Guillén, Laura
AU - Niveloni, Sonia Isabel
AU - Mauriño, Eduardo
AU - Bai, Julio César
AU - Anaya, Juan Manuel
N1 - Funding Information:
We thank all the patients and participants of this study and Liliana Daín and Rosa Liascovich for thoughtful discussions. This investigation was supported by ANPCyT (PICT 05-15051).
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/4
Y1 - 2008/4
N2 - To assess the joint contribution of interleukin 1 beta (IL-1B) and tumor necrosis factor alpha (TNFα) to the genetic risk of developing celiac disease (CD), we analyzed four biallelic polymorphisms of TNFA and IL-1B genes in 228 patients and 244 healthy controls. The individual contribution of TNFA -308A and IL-1B -511C alleles was weak (OR 1.47 and 1.66, respectively) and was null for TNFA -238 A/G and IL-1B +3953 C/T single nucleotide polymorphisms (SNPs). Due to the potential linkage disequilibrium between TNFA, human leukocyte antigen (HLA) -DQA1 and HLA-DQB1 genes, only individuals carrying DQ2 antigen (DQ2-positive) were considered to perform haplotype analyses. Two-position risk haplotypes were first defined by the combined presence of -511C and +3953T alleles for IL-1B (OR 9.402) or -308A and -238A alleles for TNFA (OR 15.389). The TNFA/IL-1B combined haplotype-stratified association analysis showed that the simultaneous presence of TNFA risk and IL-1B non-risk haplotypes (OR 13.32) but not TNFA non-risk and IL-1B risk haplotypes (OR 0.71) is associated with CD. Interestingly, our data suggest that the coexistence of both risk haplotypes seems to work synergistically (OR 29.59), which enhances the risk of developing CD.
AB - To assess the joint contribution of interleukin 1 beta (IL-1B) and tumor necrosis factor alpha (TNFα) to the genetic risk of developing celiac disease (CD), we analyzed four biallelic polymorphisms of TNFA and IL-1B genes in 228 patients and 244 healthy controls. The individual contribution of TNFA -308A and IL-1B -511C alleles was weak (OR 1.47 and 1.66, respectively) and was null for TNFA -238 A/G and IL-1B +3953 C/T single nucleotide polymorphisms (SNPs). Due to the potential linkage disequilibrium between TNFA, human leukocyte antigen (HLA) -DQA1 and HLA-DQB1 genes, only individuals carrying DQ2 antigen (DQ2-positive) were considered to perform haplotype analyses. Two-position risk haplotypes were first defined by the combined presence of -511C and +3953T alleles for IL-1B (OR 9.402) or -308A and -238A alleles for TNFA (OR 15.389). The TNFA/IL-1B combined haplotype-stratified association analysis showed that the simultaneous presence of TNFA risk and IL-1B non-risk haplotypes (OR 13.32) but not TNFA non-risk and IL-1B risk haplotypes (OR 0.71) is associated with CD. Interestingly, our data suggest that the coexistence of both risk haplotypes seems to work synergistically (OR 29.59), which enhances the risk of developing CD.
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U2 - 10.1016/j.cyto.2008.01.015
DO - 10.1016/j.cyto.2008.01.015
M3 - Article
C2 - 18346907
AN - SCOPUS:41149096930
SN - 1043-4666
VL - 42
SP - 48
EP - 54
JO - Cytokine
JF - Cytokine
IS - 1
ER -
