Genetic Background of Celiac Disease and Its Clinical Implications

Department of Pediatric Gastroenterology, University Medical Center, Utrecht, The Netherlands.
The American Journal of Gastroenterology (Impact Factor: 10.76). 02/2008; 103(1):190-5. DOI: 10.1111/j.1572-0241.2007.01471.x
Source: PubMed


Celiac disease (CD) is a complex genetic disorder with multiple contributing genes. Linkage studies have identified several genomic regions that probably contain CD susceptibility genes. The most important genetic factors identified are HLA-DQ2 and HLA-DQ8, which are necessary but not sufficient to predispose to CD. The associations found in non-HLA genomewide linkage and association studies are much weaker. This might be because a large number of non-HLA genes contributes to the pathogenesis of CD. Hence, the contribution of a single predisposing non-HLA gene might be quite modest. Practically all CD patients carry HLA-DQ2 or HLA-DQ8, while the absence of these molecules has a negative predictive value for CD close to 100%. Genetic risk profiles for CD would be helpful in clinical practice for predicting disease susceptibility and progression.

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    • "9. Neurológiai tünetek: neuropathia, ataxia, migrén, occipitalis epilepszia. is összefüggést mutat. Fogékonysági régiót főként a 2q, 5q31-33, a 11q32, 15q, 19p13 kromoszómákon valószínűsítenek [6]. Két, a teljes génállományra kiterjedő vizsgálat (genome-wide association studies: GWAS) és egy génfeltérképező program (fi ne mapping project) összesen 57 olyan non-HLA single nukleotid poliformizmust (SNP) fedezett fel, amelyek összefüggést mutatnak a coeliakia kialakulásával [7]. "
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    ABSTRACT: Genetic backround of coeliac disease has been subjects to intensive research since decades. However, only results of HLA phenotyping have been taken over to routine clinical practice. Meanwhile, data on the role of epigenetical factors in the manifestation of diseases have been emerging. In coeliac disease, there are several questions both in the fields of genetics and epigenetics yet to be answered. In this review, a cross section of current knowledge on these issues is presented with special interest regarding the future clinical applications. Orv. Hetil., 2014, 155(3), 83-88.
    Orvosi Hetilap 01/2014; 155(3):83-8. DOI:10.1556/OH.2014.29795
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    • "Celiac disease (CD) is a common, highly heritable [1], small intestinal inflammatory condition induced by wheat gluten and related proteins from rye and barley [2]. Specific risk alleles of the HLA-DQA1 and DQB1 genes encoding the DQ2 and DQ8 heterodimers appear to be necessary, but not solely responsible for development of CD [3]. These specific HLA genotypes explain approximately 40 percent of the genetic risk for CD. "
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    ABSTRACT: Celiac disease is a common small intestinal inflammatory condition induced by wheat gluten and related proteins from rye and barley. Left untreated, the clinical presentation of CD can include failure to thrive, malnutrition, and distension in juveniles. The disease can additionally lead to vitamin deficiencies, anemia, and osteoporosis. Therefore, CD potentially negatively affected fitness in past populations utilizing wheat, barley, and rye. Previous analyses of CD risk variants have uncovered evidence for positive selection on some of these loci. These studies also suggest the possibility that risk for common autoimmune conditions such as CD may be the result of positive selection on immune related loci in the genome to fight infection. Under this evolutionary scenario, disease phenotypes may be a trade-off from positive selection on immunity. If this hypothesis is generally true, we can expect to find a signal of natural selection when we survey across the network of loci known to influence CD risk. This study examines the non-HLA autosomal network of gene loci associated with CD risk in Europe. We reject the null hypothesis of neutrality on this network of CD risk loci. Additionally, we can localize evidence of selection in time and space by adding information from the genome of the Tyrolean Iceman. While we can show significant differentiation between continental regions across the CD network, the pattern of evidence is not consistent with primarily recent (Holocene) selection across this network in Europe. Further localization of ancient selection on this network may illuminate the ecological pressures acting on the immune system during this critically interesting phase of our evolution.
    PLoS ONE 07/2013; 8(7):e70564. DOI:10.1371/journal.pone.0070564 · 3.23 Impact Factor
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    • "Among the 39 genetic risk factors that have been identified in CD, the major histocompatibility complex (MHC) alleles harbour the strongest genetic association [28]. Approximately 95% of CD patients express genes encoding the MHC class II protein HLA-DQ2.5 versus 30% of the control population, and the majority of the remaining patients are HLA-DQ8 positive [29]. By presenting gluten peptides to immune cells, the HLA molecules are key players in driving the gluten-specific immune response in CD. "
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    ABSTRACT: A small subset of coeliac disease (CD) patients experiences persisting or recurring symptoms despite strict adherence to a gluten-free diet (GFD). When other causes of villous atrophy have been excluded, these patients are referred to as refractory celiac disease (RCD) patients. RCD can be divided in two types based on the absence (type I) or presence (type II) of an, usually clonal, intraepithelial lymphocyte population with aberrant phenotype. RCDI usually runs a benign course and may be difficult to be differentiated from uncomplicated, slow responding CD. In contrast, RCDII can be defined as low-grade intraepithelial lymphoma and frequently transforms into an aggressive enteropathy associated T-cell lymphoma with dismal prognosis. This paper describes the clinical characteristics of RCDI and RCDII, diagnostic approach, and the latest insights in treatment options.
    Gastroenterology Research and Practice 05/2013; 2013(1):518483. DOI:10.1155/2013/518483 · 1.75 Impact Factor
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