Biomarker Found for Celiac Patients on Gluten-Free Diet
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By LabMedica International staff writers Posted on 19 Jun 2019 |
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Representative histologic features of the small intestine. In the normal duodenal biopsy (A), the villi are elongated and the crypts relatively short. This is in contrast to the small intestinal tissue affected by celiac disease (B), which demonstrates marked villus blunting and crypt hyperplasia. (Photo courtesy of Tracy R. Ediger MD, and Ivor D. Hill, MD ChB).
Celiac disease is a complex condition, routinely treated by means of a strict gluten-free diet (GFD). One of the diagnostic challenges of this disease is that patients need to be consuming gluten so that a correct diagnosis by means of endoscopy can be made.
Celiac disease (CeD) is an immune-mediated enteropathy with a strong genetic component, where alleles encoding Human Leukocyte Antigen (HLA)-DQ2 and -DQ8 molecules account for 40% of disease heritability. A genetic, constitutive biomarker present also when the disease-triggering insult is absent would be extremely useful for the diagnosis this conditions.
Scientists associated with the University of the Basque Country (Leioa, Spain) hypothesized that merging different levels of genomic information through Mendelian Randomization (MR) could help discover genetic biomarkers useful for CeD diagnosis. MR was performed using public databases (9,451 cases and 16,434 controls) of expression quantitative trait loci (eQTL) and methylation QTL (mQTL) as exposures, and the largest CeD genome-wide association study (GWAS) conducted to date as the outcome, in order to identify potential causal genes.
The scientists identified UBE2L3, an ubiquitin ligase located in a CeD-associated region. They interrogated the expression of UBE2L3 in an independent dataset of peripheral blood mononuclear cells (PBMCs) and found that its expression is altered in CeD patients on GFD when compared to non-celiac controls. The relative expression of UBE2L3 isoforms predicts CeD with 100% specificity and sensitivity and could be used as a diagnostic marker, especially in the absence of gluten consumption.
The authors concluded that the relative expression of the isoforms of the UBE2L3 gene in the blood makes it possible to distinguish with 100% sensitivity and specificity celiac patients on a gluten-free diet. The approach used could be applicable to other diseases where diagnosis of asymptomatic patients can be complicated. The study was published on May 29, 2019, in the journal Human Molecular Genetics.
Related Links:
University of the Basque Country
Celiac disease (CeD) is an immune-mediated enteropathy with a strong genetic component, where alleles encoding Human Leukocyte Antigen (HLA)-DQ2 and -DQ8 molecules account for 40% of disease heritability. A genetic, constitutive biomarker present also when the disease-triggering insult is absent would be extremely useful for the diagnosis this conditions.
Scientists associated with the University of the Basque Country (Leioa, Spain) hypothesized that merging different levels of genomic information through Mendelian Randomization (MR) could help discover genetic biomarkers useful for CeD diagnosis. MR was performed using public databases (9,451 cases and 16,434 controls) of expression quantitative trait loci (eQTL) and methylation QTL (mQTL) as exposures, and the largest CeD genome-wide association study (GWAS) conducted to date as the outcome, in order to identify potential causal genes.
The scientists identified UBE2L3, an ubiquitin ligase located in a CeD-associated region. They interrogated the expression of UBE2L3 in an independent dataset of peripheral blood mononuclear cells (PBMCs) and found that its expression is altered in CeD patients on GFD when compared to non-celiac controls. The relative expression of UBE2L3 isoforms predicts CeD with 100% specificity and sensitivity and could be used as a diagnostic marker, especially in the absence of gluten consumption.
The authors concluded that the relative expression of the isoforms of the UBE2L3 gene in the blood makes it possible to distinguish with 100% sensitivity and specificity celiac patients on a gluten-free diet. The approach used could be applicable to other diseases where diagnosis of asymptomatic patients can be complicated. The study was published on May 29, 2019, in the journal Human Molecular Genetics.
Related Links:
University of the Basque Country
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