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    Dense Genotyping Pinpoints Numerous Common and Rare Variant Association Signals in Celiac Disease


    Jefferson Adams

    Celiac.com 02/22/2012 - A research team recently conducted a dense genotyping non-HLA risk loci previously associated with immune-mediated diseases in individuals with celiac disease. The study was conducted under the auspices of the Genetics Department, University Medical Center and University of Groningen, The Netherlands.


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    Photo: CC-Bogdan SudituThe team used variants from the 1000 Genomes Project pilot European CEU dataset, along with data from additional re-sequencing studies, to densely genotype a total of 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease and in 12,228 control subjects.

    They were able to discover thirteen new celiac disease risk loci reaching genome-wide significance. This discovery brings the number of loci known to be associated with celiac disease, including the HLA locus, to forty.

    The team found multiple independent association signals in more than one in three of the loci. This is likely due to a combination of common, low-frequency and rare genetic variants.

    Compared to earlier data, such as those from HapMap3, the large study group and the dense gene mapping made for a much higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions.

    In all, the team found that 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements.

    Finally, they defined the complex genetic architecture of the risk regions of celiac disease. They also refined the risk signals for celiac disease, which provide support for the next steps in understanding its causes.

    The research team included G. Trynka, K. A. Hunt, N. A. Bockett, J. Romanos, V. Mistry, A. Szperl, S. F. Bakker, M. T. Bardella, L. Bhaw-Rosun, G. Castillejo, E. G. de la Concha, R. C. de Almeida, K. R. Dias, C. C. van Diemen, P.C. Dubois, R. H. Duerr, S. Edkins, L. Franke, K. Fransen, J. Gutierrez, G. A. Heap, B. Hrdlickova, S. Hunt, L. P. Izurieta, V. Izzo, L. A. Joosten, C. Langford, M. C. Mazzilli, C. A. Mein, V. Midah, M. Mitrovic, B. Mora, M. Morelli, S. Nutland, C. Núñez, S. Onengut-Gumuscu, K. Pearce, M. Platteel, I. Polanco, S. Potter, C. Ribes-Koninckx, I. Ricaño-Ponce, S. S. Rich, A. Rybak, J. L. Santiago, S. Senapati, A. Sood, H. Szajewska, R. Troncone, J. Varadé, C. Wallace, V. M. Wolters, and A. Zhernakova. The study team also included B. K. Thelma, B. Cukrowska, E. Urcelay, J. R. Bilbao, M. L. Mearin, D. Barisani, J. C. Barrett, V. Plagnol, P. Deloukas, C. Wijmenga, and D. A. van Heel, who are variously affiliated with the Spanish Consortium on the Genetics of Coeliac Disease (CEGEC), the PreventCD Study Group, and the Wellcome Trust Case Control Consortium (WTCCC).

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  • About Me

    Jefferson Adams is a freelance writer living in San Francisco. He has covered Health News for Examiner.com, and provided health and medical content for Sharecare.com. His work has appeared in Antioch Review, Blue Mesa Review, CALIBAN, Hayden's Ferry Review, Huffington Post, the Mississippi Review, and Slate, among others.

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  • Related Articles

    Scott Adams
    The following was sent to me from Rio de Janeiro by Dr. José Cesar da Fonseca Junqueira. If you have any questions you can e-mail him at: cjunqueira@ax.apc.org.br
    Rio de Janeiro - 05/27/96 - Celiac Disease. A Comparative study of two periods. Junqueira JC, Calçado AC, Percope S. 1996 Federal University of Rio de Janeiro Martagão Gesteira - Institute of Pediatrics. The aim of this study was to compare cases of celiac disease diagnosed in outpatients with malabsortion cases. The study was conducted at the Pediatric Gastroenterology Service of the Pediatric Institute Martagão Gesteira at the Federal University of Rio de Janeiro Brazil. It was done in two phases: from 1975 -1984 and from 1985 - 1994 (group 1, N=31 and group 2, N=21). Patients were selected based on the results of jejunal biopsy (group IV) and the favorable reaction to a gluten free diet. Data from the first interview (age, sex, nutritional status and prevalent symptoms) were analyzed. The number of biopsies and the level of compliance with the diet were also observed. The data collected was processed in a computer using EPI INFO 6.03 (January 1996)as software. The frequency of celiac disease over the studied years was compared with international data. There were no significant differences between the two groups in our study. However, the cases free of gastroenterological symptoms (atypical celiac disease) were not observed. The average age difference between the groups (group um X=24,39 months; group 2 X=32,03) was not statistically significant. A bigger study must be carried out to prove this theory. The analysis of nutritional status of the groups reveals the existence of severely undernourished patients. The number of biopsies and the level of compliance with diet were similar in the two groups. The decrease in the number of cases as well the increase in the age of patients were observed in group 2. These phenomena were probably due to a delayed exposure to gluten and to the expansion of the period of breast feeding. Other causes should be analyzed in a bigger research program. The conclusion of this study shows that there has been no change in the clinical features of the disease and points to the need for serological screening so that the entire spectrum of the disease can be established.
    Both groups had malabsorption and were very under-nourished (over 45%). One patient was diagnosed as having Diabetes Mellitus several years after and an other one is under investigation for poliarthrites. Serological investigation is not available in our country. The final conclusion is that we must have such serological screening to know the real spectrum of the disease. Adult celiac disease is not diagnosed in our country, mainly because the adult doctors do not know the full spectrum of celiac disease.
    Ill be presenting this work as a thesis at the University on May 29, 1996.

    Jefferson Adams
    Celiac.com 09/16/2008 - Cytokines are regulatory proteins that act as mediators in the generation of an immune response. Interleukin 21 (IL-21) is on such cytokine.
    A team of Italian and British researchers recently evaluated the production of IL-21 in the intestinal mucosa of patients with untreated celiac disease. Several studies have documented the ability of IL-21's to regulate cytokine production by certain T cells. Another recent study demonstrated a connection between celiac disease and what is called the susceptibility locus in the chromosome 4q27, which harbors the IL-21 gene.
    The researchers, led by Dr. G. Monteleone at Universita Tor Vergata in Rome, set out to examine the molecular mechanisms tying IFN-gamma with celiac disease. The team found that people with celiac disease produce excess IL-21, and that IL-21 is responsible for encouraging production of interferon-gamma (IFN-gamma).
    In active celiac disease, large numbers of polarized T helper Type 1 (Th1) cells accumulate in the upper intestinal tract, where they produce large amounts of IFN-gamma. The team looked at upper bowel biopsies taken from 91 people from 22 to 54 years of age. 43 had untreated celiac disease, 12 patients had treated celiac disease, and 36 served as healthy controls. The mucosa of those with untreated celiac disease showed highly elevated IL-21 levels compared with the healthy control group (P < 0.001), while those with treated celiac disease showed the same levels of IL-21.
    When the research team blocked endogenous IL-21 in ex vivo organ cultures from untreated celiac disease patients, they saw a reduced expression of both IFN-gamma and T-bet, a master regulator of Th1 cell response.
    When the research team stimulated biopsy cultures with a peptic-tryptic digest of gliadin (PT) explants, the biopsies of patients with treated celiac disease showed elevated IL-21, while the controls showed no such elevation. The team was able to use an anti-IL-21 antibody to substantially reduce the enhancement of T-bet expression by PT (P = 0.01), whereas they saw no such reduction using a control antibody.
    These results indicate that up-regulation of IL-21 in celiac disease depends on gluten-driven active inflammation. As such, IL-21 may have a crucial role in promoting the destructive inflammation in celiac disease. If so, neutralizing the production or presence of IL-21 might offer a promising and alternative therapeutic approach in treating celiac disease, especially in treating cases of celiac disease that are unresponsive to a gluten-free diet.
    In a side note, several doctors have noted that the role of IL-21 does not seem to be exclusive to celiac disease, as the biopsies of patients with Helicobacter pylori infections, and those suffering from Crohn's disease show similar increases in IL-21 synthesis.
    Gut 2008: 57; 879-881,887-892.



    Destiny Stone
    Celiac.com 08/05/2010 - A myriad of autoimmune disordersincluding, Addison's disease, type 1 diabetes and celiac disease areclosely associated with the HLA-DR3 haplotype. However it is has beenhypothesized that alleles of other genes in linkage disequilibriumwith HLA-DRB1 also contribute to the diseases.
    Researchers at the Barbara Davis Centerfor Childhood Diabetes, University of Colorado Denver, Aurora,Colorado, conducted a study to characterize major histocompatabilitycomplex (MHC) haplotypes which put patients at high risk forAddison's disease.
    Between 1992 and 2009, eighty-sixCaucasian subjects with 21-hydroxylase autoantibody-positive ,nonautoimmune polyendocrine syndrome type 1, were genotyped forJLA-DRB1, HLA-DQB1, MICA, HLA-B, HLA-A and high density MHCsingle-nucleotide polymorphism analysis for 34.
    Measuring AD and genotype, 97% of themultiplex subjects, 60% of the simplex AD subjects and 13% of thegeneral population control group had both HLA-DR3 and HLA-B8. The study also found that 85% of the ADmultiplex subjects, 24% of the simplex patients and 1.5% of thecontrol group subjects presented with DR3/DR4 and B8. Also discovered through this study wasthat the DR3-B8 haplotype of AD subjects only 47% had HLA-A1,compared to the control subjects at 81% and the type 1 diabeticsubjects at 73%.
    Researchers of this study concludedthat severe risk for Addison's disease, specifically in multiplexfamilies, is connected to haplotypic DR3 variants in specific a part(3.8) though not all of the conserved 3.8.1 haplotype.
    Source:
    PubMed.govJClin Endocrinol Metab. 2010 Jul 14.

    Gryphon Myers
    Celiac.com 09/03/2012 - Celiac disease numbers in Western countries are currently somewhere in the 1:100 range, but this does not account for a host of non-celiac gluten intolerant people. For many, it is common knowledge that gluten and wheat intolerance manifests in a variety of forms, and not all of them are diagnosable as celiac disease. This has not prevented scientific circles from debating the existence of such non-celiac wheat sensitivities though. A double-blind placebo-controlled study spanning 2001-2011 demonstrates that wheat sensitivity exists as a distinct clinical condition, separate from celiac disease.
    Many who go to their doctors seeking a celiac disease diagnosis are disappointed when they are told that they do not have celiac disease, but the more catch-all, and less conclusive IBS, even though they have self-diagnosed and know that gluten aggravates their symptoms. Such IBS-diagnosed patients who attended the outpatient center at the Department of Internal Medicine at the University Hospital of Palermo or the Department of Internal Medicine of the Hospital of Sciacca between January 2001 and June 2011 were considered for the study.
    After a number of diagnostic inclusion and exclusion criteria were applied, 920 patients were invited to participate in the study. Patients were monitored for 2-4 weeks while on a 30g minimum wheat-containing diet, then put on a standard elimination diet (no wheat, cow's milk, eggs, tomatoes or chocolate). Any further known food sensitivities were avoided as well.
    After 4 weeks on the elimination diet, patients underwent double-blind placebo-controlled challenges, with single foods being presented at a time. Placebo and wheat (or other eliminated food) were administered for two weeks at a time, one after the other with a one week washout period in between.
    Severity of symptoms was recorded during all phases of the study. Challenges were stopped if symptoms presented, and considered positive if the symptoms were the same symptoms originally diagnosed as IBS.
    There were two control groups: 50 patients with IBS who were not classified as suffering from wheat or food sensitivities, and 100 patients who had received celiac disease diagnoses.
    Of the 920 participants, 276 (30%) suffered wheat sensitivity symptoms, became asymptomatic on elimination diet and symptomatic again during the DBPC challenge. 70 of these patients were diagnosed with wheat sensitivity alone, and two hundred and six were diagnosed with multiple food hypersensitivity. The first group of patients' symptoms resembled celiac disease, whereas the patients in the second group had symptoms that more closely resembled food allergy.
    Relevant markers to distinguish wheat sensitivity from IBS include anemia, weight loss and history of food allergy in infancy. Wheat sensitive patients also tended to have more coexistent atopic diseases.
    From this study, we know that non-celiac wheat sensitivity exists. Further studies will explore the distinction between the celiac-like and allergy-like types of the condition.
    Source:
    http://www.ncbi.nlm.nih.gov/pubmed/22825366

  • Recent Articles

    Jefferson Adams
    Celiac.com 06/23/2018 - If you’re looking for a great gluten-free Mexican-style favorite that is sure to be a big hit at dinner or at your next potluck, try these green chili enchiladas with roasted cauliflower. The recipe calls for chicken, but they are just as delicious when made vegetarian using just the roasted cauliflower. Either way, these enchiladas will disappear fast. Roasted cauliflower gives these green chili chicken enchiladas a deep, smokey flavor that diners are sure to love.
    Ingredients:
    2 cans gluten-free green chili enchilada sauce (I use Hatch brand) 1 small head cauliflower, roasted and chopped 6 ounces chicken meat, browned ½ cup cotija cheese, crumbled ½ cup queso fresco, diced 1 medium onion, diced ⅓ cup green onions, minced ¼ cup radishes, sliced 1 tablespoon cooking oil 1 cup chopped cabbage, for serving ½ cup sliced cherry or grape tomatoes, for serving ¼ cup cilantro, chopped 1 dozen fresh corn tortillas  ⅔ cup oil, for softening tortillas 1 large avocado, cut into small chunks Note: For a tasty vegetarian version, just omit the chicken, double the roasted cauliflower, and prepare according to directions.
    Directions:
    Heat 1 tablespoon oil in a cast iron or ovenproof pan until hot.
    Add chicken and brown lightly on both sides. 
    Remove chicken to paper towels to cool.
     
    Cut cauliflower into small pieces and place in the oiled pan.
    Roast in oven at 350F until browned on both sides.
    Remove from the oven when tender. 
    Allow roasted cauliflower to cool.
    Chop cauliflower, or break into small pieces and set aside.
    Chop cooled chicken and set aside.
    Heat 1 inch of cooking oil in a small frying pan.
    When oil is hot, use a spatula to submerge a tortilla in the oil and leave only long enough to soften, about 10 seconds or so. 
    Remove soft tortilla to a paper towel and repeat with remaining tortillas.
    Pour enough enchilada sauce to coat the bottom of a large casserole pan.
    Dunk a tortilla into the sauce and cover both sides. Add more sauce as needed.
    Fill each tortilla with bits of chicken, cauliflower, onion, and queso fresco, and roll into shape.
    When pan is full of rolled enchiladas, top with remaining sauce.
    Cook at 350F until sauce bubbles.
    Remove and top with fresh cotija cheese and scallions.
    Serve with rice, beans, and cabbage, and garnish with avocado, cilantro, and sliced grape tomatoes.

     

    Roxanne Bracknell
    Celiac.com 06/22/2018 - The rise of food allergies means that many people are avoiding gluten in recent times. In fact, the number of Americans who have stopped eating gluten has tripled in eight years between 2009 and 2017.
    Whatever your rationale for avoiding gluten, whether its celiac disease, a sensitivity to the protein, or any other reason, it can be really hard to find suitable places to eat out. When you’re on holiday in a new and unknown environment, this can be near impossible. As awareness of celiac disease grows around the world, however, more and more cities are opening their doors to gluten-free lifestyles, none more so than the 10 locations on the list below.
    Perhaps unsurprisingly, the U.S is a hotbed of gluten-free options, with four cities making the top 10, as well as the Hawaiian island of Maui. Chicago, in particular, is a real haven of gluten-free fare, with 240 coeliac-safe eateries throughout this huge city. The super hip city of Portland also ranks highly on this list, with the capital of counterculture rich in gluten-free cuisine, with San Francisco and Denver also included. Outside of the states, several prominent European capitals also rank very highly on the list, including Prague, the picturesque and historic capital of the Czech Republic, which boasts the best-reviewed restaurants on this list.
    The Irish capital of Dublin, meanwhile, has the most gluten-free establishments, with a huge 330 to choose from, while Amsterdam and Barcelona also feature prominently thanks to their variety of top-notch gluten-free fodder.
    Finally, a special mention must go to Auckland, the sole representative of Australasia in this list, with the largest city in New Zealand rounding out the top 10 thanks to its 180 coeliacsafe eateries.
    The full top ten gluten-free cities are shown in the graphic below:
     

    Jefferson Adams
    Celiac.com 06/21/2018 - Would you buy a house advertised as ‘gluten-free’? Yes, there really is such a house for sale. 
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    Still, the signs seem to be working. D'elena had fielded six offers within a few days of listing the west Phoenix home.
    "Buying can sometimes be the most stressful thing you do in your entire life so why not have some fun with it," he said. 
    What do you think? Clever? Funny?
    Read more at Arizonafamily.com.

    Advertising Banner-Ads
    Bakery On Main started in the small bakery of a natural foods market on Main Street in Glastonbury, Connecticut. Founder Michael Smulders listened when his customers with Celiac Disease would mention the lack of good tasting, gluten-free options available to them. Upon learning this, he believed that nobody should have to suffer due to any kind of food allergy or dietary need. From then on, his mission became creating delicious and fearlessly unique gluten-free products that were clean and great tasting, while still being safe for his Celiac customers!
    Premium ingredients, bakeshop delicious recipes, and happy customers were our inspiration from the beginning— and are still the cornerstones of Bakery On Main today. We are a fiercely ethical company that believes in integrity and feels that happiness and wholesome, great tasting food should be harmonious. We strive for that in everything we bake in our dedicated gluten-free facility that is GFCO Certified and SQF Level 3 Certified. We use only natural, NON-GMO Project Verified ingredients and all of our products are certified Kosher Parve, dairy and casein free, and we have recently introduced certified Organic items as well! 
    Our passion is to bake the very best products while bringing happiness to our customers, each other, and all those we meet!
    We are available during normal business hours at: 1-888-533-8118 EST.
    To learn more about us at: visit our site.

    Jefferson Adams
    Celiac.com 06/20/2018 - Currently, the only way to manage celiac disease is to eliminate gluten from the diet. That could be set to change as clinical trials begin in Australia for a new vaccine that aims to switch off the immune response to gluten. 
    The trials are set to begin at Australia’s University of the Sunshine Coast Clinical Trials Centre. The vaccine is designed to allow people with celiac disease to consume gluten with no adverse effects. A successful vaccine could be the beginning of the end for the gluten-free diet as the only currently viable treatment for celiac disease. That could be a massive breakthrough for people with celiac disease.
    USC’s Clinical Trials Centre Director Lucas Litewka said trial participants would receive an injection of the vaccine twice a week for seven weeks. The trials will be conducted alongside gastroenterologist Dr. James Daveson, who called the vaccine “a very exciting potential new therapy that has been undergoing clinical trials for several years now.”
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    Read more at the website for Australia’s University of the Sunshine Coast Clinical Trials Centre.

    Source:
    FoodProcessing.com.au