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NIH Consensus and State-of-the-science...To provide health care providers, patients, and the general public with a responsible assessment of currently available data regarding celiac disease.
OBJECTIVE
To provide health care providers, patients, and the general public with a responsible assessment of currently available data regarding celiac disease.
PARTICIPANTS
A non-DHHS, non-advocate 13-member panel representing the fields of internal medicine, gastroenterology, medical genetics, pathology, endocrinology, nutrition, and a consumer representative. In addition, 19 experts in related fields presented data to the panel and to the conference audience.
EVIDENCE
Presentations by experts; a systematic review of the medical literature provided by the Agency for Healthcare Research and Quality; and an extensive bibliography of celiac disease research papers, prepared by the National Library of Medicine. Scientific evidence was given precedence over clinical anecdotal experience.
CONFERENCE PROCESS
Answering pre-determined questions, the panel drafted its statement based on scientific evidence presented in open forum and on the published scientific literature. The draft statement was read in its entirety on the final day of the conference and circulated to the audience for comment. The panel then met in executive session to consider the comments received, and released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government.
CONCLUSIONS
Celiac disease is an immune-mediated intestinal disorder with protean manifestations. Celiac disease is common, affecting 0.5 to 1.0 percent of the general population of the United States, but is greatly underdiagnosed. There are now specific and sensitive serologic tests available to aid in diagnosis that need to be more widely applied. The treatment of celiac disease remains a lifelong gluten-free diet, which results in remission for most individuals. The classic presentation of diarrhea and malabsorption is less common, and atypical and silent presentations are increasing. Most individuals are being seen by primary care providers and a broad range of specialists. Therefore, heightened awareness of this disease is imperative. Education of physicians, registered dietitians, and other health providers is needed. The panel recommends the following: (1) Education of physicians, dietitians, nurses, and the public about celiac disease by a trans-National Institutes of Health (NIH) initiative, to be led by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), in association with the Centers for Disease Control and Prevention; (2) Standardization of serologic tests and pathologic criteria for the diagnosis of celiac disease; (3) Adoption of a standard definition of a gluten-free diet based on objective evidence such as that being developed by the American Dietetic Association; (4) Development of an adequate testing procedure for gluten in foods and definition of standards for gluten-free foods in the United States to lay the foundation for rational food labeling; (5) Formation of a federation of celiac disease societies, celiac disease interest groups, individuals with celiac disease and their families, physicians, dietitians, and other health care providers for the advancement of education, research, and advocacy for individuals with celiac disease.
Topics: Autoantibodies; Biomarkers; Biopsy; Celiac Disease; Evidence-Based Medicine; Glutens; HLA-DQ Antigens; Humans; Immunoglobulin A; Interdisciplinary Communication; Intestinal Mucosa; Transglutaminases; United States
PubMed: 17308551
DOI: No ID Found -
BMC Medical Genetics Jul 2006N-acetyltransferase 2 (NAT2) metabolizes arylamines and hydrazines moeities found in many therapeutic drugs, chemicals and carcinogens. The gene encoding NAT2 is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
N-acetyltransferase 2 (NAT2) metabolizes arylamines and hydrazines moeities found in many therapeutic drugs, chemicals and carcinogens. The gene encoding NAT2 is polymorphic, thus resulting in rapid or slow acetylator phenotypes. The acetylator status may, therefore, predispose drug-induced toxicities and cancer risks, such as bladder, colon and lung cancer. Indeed, some studies demonstrate a positive association between NAT2 rapid acetylator phenotype and colon cancer, but results are inconsistent. The role of NAT2 acetylation status in lung cancer is likewise unclear, in which both the rapid and slow acetylator genotypes have been associated with disease.
METHODS
We investigated three genetic variations, c.481C>T, c.590G>A (p.R197Q) and c.857G>A (p.G286E), of the NAT2 gene, which are known to result in a slow acetylator phenotype. Using validated PCR-RFLP assays, we genotyped 243 healthy unrelated Caucasian control subjects, 92 colon and 67 lung cancer patients for these genetic variations. As there is a recent meta-analysis of NAT2 studies on colon cancer (unlike in lung cancer), we have also undertaken a systematic review of NAT2 studies on lung cancer, and we incorporated our results in a meta-analysis consisting of 16 studies, 3,865 lung cancer patients and 6,077 control subjects.
RESULTS
We did not obtain statistically significant differences in NAT2 allele and genotype frequencies in colon cancer patients and control group. Certain genotypes, however, such as [c.590AA+c.857GA] and [c.590GA+c.857GA] were absent among the colon cancer patients. Similarly, allele frequencies in lung cancer patients and controls did not differ significantly. Nevertheless, there was a significant increase of genotypes [c.590GA] and [c.481CT+c.590GA], but absence of homozygous c.590AA and [c.590AA+c.857GA] in the lung cancer group. Meta-analysis of 16 NAT2 studies on lung cancer did not evidence an overall association of the rapid or slow acetylator status to lung cancer. Similarly, the summary odds ratios obtained with stratified meta-analysis based on ethnicity, and smoking status were not significant.
CONCLUSION
Our study failed to show an overall association of NAT2 genotypes to either colon or lung cancer risk.
Topics: Arylamine N-Acetyltransferase; Case-Control Studies; Colonic Neoplasms; Gene Frequency; Genetic Predisposition to Disease; Humans; Lung Neoplasms; Male; Polymorphism, Single Nucleotide; White People
PubMed: 16827944
DOI: 10.1186/1471-2350-7-58 -
Alimentary Pharmacology & Therapeutics Jul 2006With the appreciation of the high prevalence of coeliac disease there is increasing use of serology in screening asymptomatic people and testing those with suggestive... (Review)
Review
BACKGROUND
With the appreciation of the high prevalence of coeliac disease there is increasing use of serology in screening asymptomatic people and testing those with suggestive features.
AIM
To compare the sensitivities and specificities of the endomysial antibody and the tissue transglutaminase antibody tests.
METHODS
Using electronic databases a search was made for relevant papers using the terms tissue transglutaminase and endomysial antibody.
RESULTS
Both the endomysial antibody and tissue transglutaminase antibody have very high sensitivities (93% for both) and specificities (>99% and >98% respectively) for the diagnosis of typical coeliac disease with villous atrophy. Human recombinant tissue transglutaminase performs much better than guinea pig tissue transglutaminase. Review of studies comparing endomysial antibody with human recombinant tissue transglutaminase antibody shows that endomysial antibody more often has a higher specificity and human recombinant tissue transglutaminase antibody more often has a higher sensitivity.
CONCLUSION
The human recombinant tissue transglutaminase antibody is the preferred test for screening asymptomatic people and for excluding coeliac disease in symptomatic individuals with a low pretest probability (i.e. <25%) for coeliac disease. Furthermore, it has a number of practical and financial advantages. If the pretest probability is >25%, biopsy is preferred as the post-test probability of coeliac disease with a negative test is still >2%.
Topics: Antibodies; Celiac Disease; Humans; Immunologic Tests; Sensitivity and Specificity; Transglutaminases
PubMed: 16803602
DOI: 10.1111/j.1365-2036.2006.02967.x -
BMC Medical Genetics Mar 2006Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this neural death is unknown, but genetic predisposition and environmental factors may cause the disease. Sequence variations in N-acetyltransferase 2 (NAT2) gene leading to slow acetylation process have been associated with PD, but results are contradictory.
METHODS
We analyzed three NAT2 genetic variations, c.481C>T, c.590G>A (p.R197Q) and c.857G>A (p.G286E), which are known to result in a slow acetylator phenotype. Using validated PCR-RFLP assays, we genotyped 243 healthy unrelated Caucasian control subjects and 124 PD patients for these genetic variations. Further, we have undertaken a systematic review of NAT2 studies on PD and we incorporated our results in a meta-analysis consisting of 10 studies, 1,206 PD patients and 1,619 control subjects.
RESULTS
Overall, we did not find significant differences in polymorphic acetylation genotypes in PD and control subjects. In the meta-analysis of slow acetylators from 10 studies and representing 604/1206 PD vs. 732/1619 control subjects, a marginally significant odds ratio (OR) of 1.32 (95% CI 1.12-1.54, p < 0.05) was obtained. Re-analysis of the data to exclude the only two studies showing positive association of slow acetylators to PD, resulted in a non-significant OR (1.07, 95% CI 0.9-1.28). Furthermore, meta-analysis of studies for c.590G>A, where both allele and genotype frequencies in PD vs. control subjects were analyzed, did not give significant summary odds ratios as well.
CONCLUSION
We found little evidence for differences in polymorphic acetylation genotypes in PD and control subjects. Results of the meta-analyses did not also provide conclusive evidence for an overall association of NAT2 slow acetylator genotypes to PD.
Topics: Arylamine N-Acetyltransferase; Case-Control Studies; Gene Frequency; Genetic Predisposition to Disease; Humans; Parkinson Disease; Polymorphism, Single Nucleotide
PubMed: 16571112
DOI: 10.1186/1471-2350-7-30