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Celiac.com 03/20/2017 - Researchers really do not have really good data on rates of celiac disease in the general population of children in the United States. A team of researchers recently set out to estimate the cumulative incidence of celiac disease in adolescents born in the Denver metropolitan area. The research team included Edwin Liu, Fran Dong, MS, Anna E. Barón, PhD, Iman Taki, BS, Jill M. Norris, MPH, PhD, Brigitte I. Frohnert, MD, PhD, Edward J. Hoffenberg, MD, and Marian Rewers, MD, PhD. Their team collected data on HLA-DR, DQ genotypes of 31,766 infants, born from 1993 through 2004 at St. Joseph’s Hospital in Denver, from the Diabetes Autoimmunity Study in the Young. For up to 20 years, the researchers followed subjects with susceptibility genotypes for celiac disease and type 1 diabetes for development of tissue transglutaminase autoantibodies (tTGA). The team was looking for patients who developed either celiac disease autoimmunity (CDA) or celiac disease, and they defined CDA as persistence of tTGA for at least 3 months or development of celiac disease. Marsh 2 or greater lesions in biopsies or persistent high levels of tTGA, indicated celiac disease. For each genotype, the team assessed cumulative incidence of CDA and celiac disease. To estimate the cumulative incidence in the Denver general population, they weighted outcomes by each genotype, based on the frequency of each of these genotypes in the general population. They found that, of 1.339 patients they studied, 66 developed CDA and met criteria for celiac disease, while 46 developed only CDA. Seropositivity for tTGA resolved spontaneously, without treatment, in 21 of the 46 patients with only CDA (46%). The team estimated the total incidence for CDA in the Denver general population at 5, 10, and 15 years of age was 2.4%, 4.3%, and 5.1% respectively; incidence values for celiac disease were 1.6%, 2.8%, and 3.1%, respectively. This 20-year prospective study of 1.339 children with genetic risk factors for celiac disease showed the total incidence of CDA and celiac disease to be high within the first 10 years. Although more than 5% of children may experience a period of CDA, that is, persistently high celiac autoantibodies, not all of them develop celiac disease or require gluten-free diets. Sources: Gastroenterology.DOI: http://dx.doi.org/10.1053/j.gastro.2017.02.002 gastrojournal.org
Jefferson Adams posted an article in Celiac Disease & Gluten Intolerance ResearchCeliac.com 04/11/2016 - Growing evidence suggests that long noncoding RNAs (lncRNAs) play an important role in gene expression, especially that which influences inflammation. For example, researchers recently found that one lncRNA, lnc13, suppresses inflammatory gene expression in macrophages by interacting with proteins that regulate chromatin accessibility. Reduced levels of lnc13 in intestinal tissue from individuals with celiac disease suggests that lnc13 might also play a role in the development of immune-mediated diseases. In a recent issue of Science, a research team reports on the identification and characterization of a lncRNA, lnc13, that harbors a celiac disease–associated haplotype block and represses expression of certain inflammatory genes under homeostatic conditions. The research team included Ainara Castellanos-Rubio, Nora Fernandez-Jimenez, Radomir Kratchmarov, Xiaobing Luo, Govind Bhagat, Peter H. R. Green, Robert Schneider, Megerditch Kiledjian, Jose Ramon Bilbao, and Sankar Ghosh. They are variously affiliated with the Department of Microbiology and Immunology, the Department of Pathology and Cell Biology, and the Center for Celiac Disease, Department of Medicine at Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA; the Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country (UPV-EHU), at BioCruces Research Institute in Leioa, Basque Country, Spain; the Alexandria Center for Life Sciences, New York University School of Medicine, New York, NY, USA; and with the Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, USA. Their article describes how Lnc13 regulates gene expression by binding to hnRNPD, a member of a family of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). Upon stimulation, lnc13 levels decrease, thereby allowing increased expression of the repressed genes. The fact that Lnc13 levels are substantially decreased in small intestinal biopsy samples from patients with celiac disease suggests that down-regulation of lnc13 may contribute to the inflammation associated with celiac disease. Furthermore, the lnc13 disease-associated variant binds hnRNPD less efficiently than its wild-type counterpart, thus helping to explain how these single-nucleotide polymorphisms contribute to celiac disease. This discovery could lead to future treatment methods for celiac disease. Source: Science 01 Apr 2016: Vol. 352, Issue 6281, pp. 91-95. DOI: 10.1126/science.aad0467
Jefferson Adams posted an article in Celiac Disease & Gluten Intolerance ResearchCeliac.com 04/22/2011 - A research team recently set out to examine multiple independent variants in 6q21-22 associated with susceptibility to celiac disease in the Dutch, Finnish and Hungarian populations. The study team included Elisabet Einarsdottir, Marianna R Bevova, Alexandra Zhernakova, Alienke Monsuur, Lotta LE Koskinen, Ruben van't Slot, Chris Mulder, M Luisa Mearin, Ilma R Korponay-Szabo, Katri Kaukinen, Kalle Kurppa, Juha Kere, Markku Mäki, Cisca Wijmenga and Päivi Saavalainen. Studies in Dutch, Finnish and Hungarian populations have shown that a locus on chromosome 6q21-22 carries higher susceptibility to celiac disease. This same locus has previously been associated with susceptibility to other autoimmune diseases such as Crohn's disease and type 1 diabetes. The study team conducted fine mapping on 446 independent individuals with celiac disease and 641 control subjects of Dutch origin. The team tested 872 tagging single-nucleotide polymorphisms (SNPs) in a 22â€‰Mb region of chromosome 6. To identify risk variants in this region, the team followed up on the 12 most promising SNPs in 2071 individuals from 284 Finnish and 357 Hungarian celiac disease families. Numerous markers in the region showed strong associations with celiac disease in the Dutch material. Two SNPs, rs9391227 and rs4946111, showed strong association with celiac disease in the Finnish population. The rs9391227 connection is the strongest such connection yet found in the Finnish (P=0.003, OR 0.66), as well as the combined Dutch, Finnish and Hungarian populations (P=3.6 Ã— 10âˆ’5, OR 0.76). The rs9391227 site is located downstream from the HECT domain and ankyrin repeat containing, E3 ubiquitin protein ligase 1 (HACE1) gene and is contained within a region of strong linkage disequilibrium enclosing HACE1. A meta-analysis of the three populations showed two additional independent, susceptibility variants in the 6q21-22 region. The team confirmed the 6q21-22 region as a celiac disease susceptibility locus; one that is independently associated with a number of other conditions, and which may implicate ubiquitin-pathways in celiac disease susceptibility. Source: European Journal of Human Genetics , (16 February 2011) | doi:10.1038/ejhg.2011.2