TNF α and LT α gene polymorphisms as additional markers of celiac disease susceptibility in a DQ2-positive population

Abstract

TNFalpha and TNFbeta, or linfotoxin (LTalpha), are two molecules playing an important role in inflammation. Their genes map on Chromosome 6, between the HLA class II and class I loci. Polymorphisms in, or near, TNF genes have been associated with susceptibility to several autoimmune diseases. Studies of TNF genes in celiac disease (CD) have presented contradictory results. We have assessed the role of TNFalpha and linfotoxin alpha (TNFbeta) in CD and their relative value as CD markers in addition to the presence of DQ2. The TNFA -308 polymorphism and the polymorphism at the first intron of the LTA gene were typed in CD patients and healthy controls and the results were correlated with the presence of DQ2. Significant differences were found in genotype and allele frequencies for the TNFA and LTA genes between CD patients and controls, with an increase in the presence of the TNFA*2 and LTA*1 alleles in CD patients. These differences increase when DQ2-positive CD patients and DQ2-positive controls are compared. In DQ2-positive individuals, allele 2 (A) in position -308 of the promoter of TNFA and allele 1 (G) of the NcoI RFLP in the first intron of LTA are additional risk markers for CD.

IL-10 polymorphisms are associated with early-onset celiac disease and severe mucosal damage in patients of Caucasian origin

“…Comparable frequencies in the polymorphisms in celiacs and population controls have been found also by Wolley et al, 25 who recently evaluated a series of Finnish CD patients using a family-based approach, thus supporting the idea that these polymorphisms per se do not provide an increased susceptibility to CD. The frequency of the Ϫ308A allele observed in our series is similar to that observed in other patients from the Mediterranean area, 21,22 but lower than that reported in Irish and Swedish series. 19,23 However, in our population, no significant difference could be observed when patients and population controls were stratified according to the presence of DQ2, similarly to what reported by Polvi et al 20 and Wolley et al 25 To assess whether cytokine polymorphisms could affect the clinical manifestations of celiac disease we performed a multivariate analysis, considering also the possible combined genotypes.…”

“…19 -25 Moreover, very few studies have subdivided celiac patients according to their characteristics and, even in this case, only HLA class II alleles or antibody production have been considered. [22][23][24]26 The aim of this study was to compare the prevalence of polymorphisms of some pro-and anti-inflammatory cytokines genes in a large series of Italian celiac patients and population controls, and to analyze their possible relationship with different clinical parameters.…”

Defining the contribution of the HLA region to cis DQ2-positive coeliac disease patients

“…16,17 In addition, independent association of a single-nucleotide polymorphism (SNP) in the TNF gene region has been reported by several groups. [18][19][20][21] These results indicate the possibility of additional HLA risk loci in the TNF/MIC gene region. However, there is a possibility that a SNP conferring increased disease risk may not be detected by the association of nearby microsatellite markers because of their high mutation rate.…”

“…However, it has been suggested that non-class II loci also predispose to coeliac disease, independently of DQ2. [15][16][17][18][19][20][21] The aim of this study was to test whether there was evidence for the presence of additional HLA susceptibility loci for coeliac disease on DQ2-positive haplotypes from patients of Dutch origin. In all, 16 markers, covering the entire HLA region and flanking regions, were genotyped in simplex coeliac disease and in control families.…”

The Role of Cytotoxic T-Lymphocyte Associated Antigen 4 (CTLA4) +49A/G and Tumor Necrosis Factor Alpha (TNF-.ALPHA.) -308G/A Polymorphism in the Development of Celiac Disease in Jordanian Patients

“…14) A number of studies demonstrated a significant association of this polymorphism with CD in different populations. [15][16][17][18][19][20][21] The aim of this study is to analyze and to test the role of CTLA4 +49A/G and TNF-α −308G/A polymorphisms in the development of CD in Jordanian patients.…”