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    New Methods Help Researchers to Understand Gene Mutations for Celiac and Other Diseases


    Jefferson Adams

    Celiac.com 06/08/2012 - In a new study, researchers at Brigham and Women's Hospital (BWH) addressed whether the genetic risk of the most common medical conditions, including celiac disease, stems from many rare mutations that each confer a high degree of risk in various people, or from common differences throughout the genome that modestly influence risk.


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    Photo: CC--Certified SuThey used data and new analysis tools to assess new methods to better understand gene mutations for celiac and three other diseases, rheumatoid arthritis, coronary artery disease and myocardial infarction (heart attack); and type 2 diabetes.

    The researchers developed a new statistical method that used what is called "polygenic risk score analysis," to estimate the heritable genetic markers of these diseases that is explained by common differences across the genome.

    The method makes use of data from earlier genome-wide association studies, or GWAS, an approach used to scan DNA samples for common genetic markers seen throughout the population—called SNPs (single nucleotide polymorphisms).

    For rheumatoid arthritis, the team used computer simulations to show that the underlying genetic risk is largely due to many common alleles rather than rare mutations.

    They observed similar results for celiac disease (43 percent), myocardial infarction (48 percent) and type 2 diabetes (49 percent).

    "What is remarkable," says senior author Robert Plenge, MD, PhD, BWH director of Genetics and Genomics in the Division of Rheumatology, Immunology and Allergy, "is that our statistical model was broadly applicable to several common diseases, not just rheumatoid arthritis...Our study provides a clear strategy for discovering additional risk alleles for these and likely many other common diseases."

    According to the researchers, these methods can be applied to other genome-wide datasets (e.g., GWAS or whole genome sequencing) to estimate the degree to which there is a genetic component.

    Source:

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    Guest JOANMARIE JOHNSON

    Posted

    As a Native American celiac/diabetic I am also concerned about the antibiotics and hormones that are being added to beef, along with the beef being turned into cannibals. Who made that nutty decision? Good unintended consequences. Wouldn't that be adding to the weight problems we are seeing? Most tribes that are going back to the diet we were eating before the Europeans arrived en-mass are reducing the diabetes... just a thought.

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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
    Celiac.com 03/26/2007 - In is known that increased duodenal intraepithelial lymphocytes (IEL) are more common in celiac patients with Helicobacter pylori gastritis (H. pylori) than in those celiacs without Helicobacter pylori. It is also known that the elimination of Helicobacter pylori can reverse this problem. The study was motivated by the following two hypotheses:
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    Three test subjects who were positive for Helicobacter pylori, and 12 who were negative (a total of 15 test subjects), presented with lymphocytic gastritis.
    Overall, a greater proportion of Helicobacter pylori-negative patients had severe villous atrophy (p
    Regardless of their initial Helicobacter pylori status, all subjects showed marked improvement of duodenal aspects following a gluten-free diet (p
    With the exception of the intraepithelial lymphocytes (IEL), which returned to normal in two Helicobacter pylori-positive patients, and in ten Helicobacter pylori-positive patients, gastric variables remained unchanged.
    The study concludes that Helicobacter pylori gastritis is not related to the clinical features of celiac disease, and that a gluten-free diet is equally effective for both groups.
    The study also notes that the inflammatory and structural changes to the mucosal architecture that are associated with celiac disease might eclipse some of the signs of lymphocytosis induced by Helicobacter pylori gastric infection.
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    Am J Gastroenterol. 2006;101(8):1880-1885.

    Jefferson Adams
    Celiac.com 05/08/2007 - For people with celiac disease, accurate and comprehensive information on maintaining a healthy, high-level quality of life can be difficult to find. Research is particularly sketchy with respect to factors that have a negative impact on health and quality of life for adults with celiac disease.
    Factors that have a negative impact on health and quality of life are often modifiable through changes in diet, or adjustments in treatment. Thus researchers are motivated to identify which celiac patient groups are at risk of being impacted in a negative way, and to determine which adjustments might bring positive results.
    In an effort to refine treatment approaches and improve the lives of patients with celiac disease, clinical researchers in Gastroenterology have become increasingly interested in health-related quality of life issues as primary or secondary endpoints in their studies.
    A recent study published online in Medscape Today suggests that, in addition to physical and mental co-morbidities, a failure to sustain a gluten-free diet and disappointment with doctor-patient communication are also important factors associated with health-related quality of life concerns in people with celiac disease.

    Motivated by inconsistencies in available data, a team of German researchers made up of Drs. W. Häuser, A. Stallmach, W. F. Caspary, and J. Stein, set out to evaluate the various predictors for reduced health-related quality of life in adult patients with celiac disease.
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    Mental disorder (ß = 2.5; OR = 11.9, P < 0.001), physical co-morbidities (ß = -0.26; OR = 0.77, P = 0.004) and younger age at diagnosis (ß = -0.10; OR = 0.91, P = 0.05) predicted a reduced mental summary score of the SF-36 Scale.
    Mental disorder (ß = 0.90; OR = 2.5, P = 0.03), non-compliance with gluten-free diet (ß = 0.44; OR = 1.6, P = 0.009), active medical co-morbidities (ß = -0.28; OR = 0.76, P = 0.007) and dissatisfaction with doctor–patient communication (ß = 0.55; OR = 1.7, P = 0.03) were associated with reduced Celiac Disease Questionnaire scores.
    In adult patients with celiac disease, the following factors were associated with reduced health-related quality of life: female gender, younger age at diagnosis, newly diagnosed patients, latency of diagnosis, failure to follow a gluten-free diet, anxiety and somatic and psychiatric co-morbidity.
    Until this study, attempts to measure health status in patients with celiac disease relied on generic health-related quality of life methods, rather than validated, disease specific instruments, and thus the relative predictive value of these variables had not been fully assessed.
    Aliment Pharmacol Ther. 2007;25(5):569-578.
     

    Jefferson Adams
    Celiac.com 04/09/2008 - Do your chances of developing celiac disease vary depending on which parent is passing on the genes? A new study says yes.
    According to the results of a recent study, depending on whether the gene is inherited from the father or the mother, and depending on the gender of the child, data suggest that there could be some variance in rates at which the gene is inherited, along with some variance in the rates of celiac disease.
    An Italian research team set out to examine risk differences for developing celiac disease between males and females. The research team was made up of Francesca Megiorni, B.Sc., Barbara Mora, B.Sc., Margherita Bonamico, M.D., Maria Barbato, M.D., Monica Montuori, M.D., Franca Viola, M.D., Simonetta Trabace, B.Sc., and Maria C. Mazzilli, B.Sc.
    HLA typing in celiac disease is mainly considered for its negative predictive value, as people who do not carry the DQ predisposing molecules are unlikely to develop the disease. Celiac disease occurs twice as often in women as it does in men. In order to learn more about why this might be, the team of researchers recently performed genotyping for HLA-DRB1, DQA1, and DQB1 loci on 281 female and 156 male pediatric celiac patients, 292 nuclear families, and 551 controls. The team then evaluated and compared the odds ratio, parental origin of the disease-associated haplotypes, and transmission ratio distortion between male and female patients.
    Female patients more frequently exhibited DQ2/DQ8 compared to male patients (94% F, 85% M; P = 1.6 Å~ 10−3). The HLA typing test carried a calculated negative predictive value of 99.1% for females and 90.5% for men. Interestingly, the bulk of the 39 DQ2/DQ8 negative cases were male. Looking at the origins of the DQ2 haplotype, the research team noted that 61% of female patients and 42% of male patients carried a paternal combination (P = 0.02).
    Looking at the results of the transmission disequilibrium test (TDT) the team noted a major distortion in the DR3-DQ2 transmission from fathers to daughters. Among those patients that are DQ2/DQ8 positive, females showed a higher prevalence of celiac disease than did male patients, with a ratio of 1.8 to 1. Of those patients that were DQ2/DQ8 negative there was a slight tip toward the males, with a ratio of .7 to 1.
    The high prevalence of celiac disease in DQ2/DQ8 positive females only applied to females that had inherited the DQ2 haplotype from the father. The results of the study indicate that the sex of the parent supplying the HLA genes may play a role in susceptibility to celiac disease, along with a different effect of parent-specific epigenetic modifications in the two genders.
    In all, male patients developed celiac disease more frequently than female patients in absence of HLA predisposing dimmers, but this was due to the occurrence of two DQB1 susceptible alleles that seem to increase the disease risk for males. The results lead the research team to believe that the presence of DQ2 and/or DQ8 molecules is a stronger risk factor in females than in males (ORF = 40.5, ORM = 14.1). Additionally, the results also indicate that HLA typing, which is mainly considered for its negative predictive value in celiac disease, is of greater importance in the testing of females than in males, with calculated negative predictive value of 99.1% and 90.5%, respectively, which points to the need to factor gender into the calculation of disease risk.
    These findings, taken together with the revelation that inheritance of a paternal DQ2 haplotype led to celiac predominance in daughters, show that HLA genes play a role in the disease sex bias, and imply a potentially different effect of parent-speciï¬c epigenetic modiï¬cations in the two genders.
    Am J Gastroenterol 2007; 102:1–7


    Jefferson Adams
    Celiac.com 10/31/2014 - The relationship between the risk of celiac disease and both the age at which gluten is introduced to a child’s diet and a child’s early dietary pattern is unclear.
    A team of researchers set out to examine how the introduction of dietary gluten and HLA status impact the risk of celiac disease in children.
    The research team included Elena Lionetti, M.D., Stefania Castellaneta, M.D., Ruggiero Francavilla, M.D., Ph.D., Alfredo Pulvirenti, Ph.D., Elio Tonutti, M.D., Sergio Amarri, M.D., Maria Barbato, M.D., Cristiana Barbera, M.D., Graziano Barera, M.D., Antonella Bellantoni, M.D., Emanuela Castellano, M.D., Graziella Guariso, M.D., Maria Giovanna Limongelli, M.D., Salvatore Pellegrino, M.D., Carlo Polloni, M.D., Claudio Ughi, M.D., Giovanna Zuin, M.D., Alessio Fasano, M.D., and Carlo Catassi, M.D., M.P.H.
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    Other variables, including breast-feeding, were not associated with the development of celiac disease.
    So, the short take away here is that, according to this study, neither delayed introduction of gluten nor breast-feeding had any effect on celiac disease rates among at-risk infants. However, children who experienced later introduction of gluten showed a delay in the onset of disease.
    Lastly, the important predictor of disease was having a high-risk HLA genotype.
    Source:
    N Engl J Med 2014; 371:1295-1303October 2, 2014. DOI: 10.1056/NEJMoa1400697

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    Source:
    PLoS Med. 2018 Feb; 15(2): e1002507. doi:  10.1371/journal.pmed.1002507

    Jefferson Adams
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    Source:
    BMC Pediatrics

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    Read more at azcentral.com.