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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Coeliac disease in the Nord-Trøndelag Health Study

Alternative title: Cøliaki i Helseundersøkelsen i Nord-Trøndelag (HUNT)

Awarded: NOK 8.6 mill.

Coeliac disease is a prevalent disorder with unknown consequences and causes. In this project, we aim to identify the prevalence of coeliac disease in the general population and the consequences and causes of the disease. We have found that about 1.5% of the general population has coeliac disease, but many individuals were unaware that they had the disease. In coeliac patients, dietary gluten in wheat, barley and rye leads to inflammation and destruction of the mucosa of the small intestines. Typically, patients with coeliac disease have diarrhoea and weight loss, or poor growth in children, due to poor absorption of nutrients by the damaged intestines. However, the disease might have vague and diffuse symptoms, which makes it difficult to diagnose. The disease is closely related to two genes (HLA-DQ2 and HLA-DQ8), but only some of the individuals with these genes actually develop the disease, so there must be unknown causes triggering the onset of the disease. In this project, we have screened for coeliac disease in a large population-based health study in Norway, the Nord-Trøndelag Health Study (HUNT), where all adult residents of Nord-Trøndelag County have been invited. All participants in the fourth HUNT study (HUNT4) have been screened for coeliac disease and we have establish the total prevalence of the disease in the general population, including the previously undiagnosed individuals with coeliac disease. Further, we will identify the consequences of the disease in this population, based on self-reported questionnaires and linkage to national health registries. By using questionnaire data, blood samples and genetic data from previous HUNT studies performed over the past 30 years, we will assess possible triggering and predictive environmental and genetic factors that might cause of the disease. So far in the project we have established a new serological test for coeliac disease. This test has been run on blood samples from all the 56,000 participants in HUNT4. Participants with a positive test, have been summoned for additional tests at Levanger Hospital, including tissue samples from the small intestine to confirm the diagnosis. At the same visit, the participants have reported on their health through extensive written questionnaires, and we have collected additional blood, saliva and faecal samples. In addition, the participants have had bone density measurements and dental x-rays performed. The material collected will be used to identify the consequences of the disease and search for possible triggers or predictive factors. We have linked to the participants hospital journal records and identified HUNT4 participants with a known coeliac disease, who were not identified by the serological test. By using these data, we have included all individuals with coeliac disease among the HUNT4 participants. We have also linked to national health registries to collect data on other diseases of the participants in HUNT4 with coeliac disease and compare this to the diseases of the HUNT4 participants without coeliac disease. The material we collect from all these sources will be used to assess the consequences and causes of the disease.

Coeliac disease is characterized by chronic inflammation of the small intestines and destruction of the mucosa, leading to malabsorption. The classical symptoms are diarrhoea and weight loss or growth failure. Coeliac disease is highly prevalent in northern Europeans and possibly also worldwide. The current understanding of coeliac disease is as a chronic immune disorder precipitated by exposure to dietary gluten in genetically predisposed individuals. Gluten is present in wheat, barley and rye. Coeliac disease is closely associated with two genes (HLA-DQ2 and HLA-DQ8). However, these genes only explain some of the known heritability of the disease, so other genes must also be involved. In addition, only some HLA-DQ2 or HLA-DQ8 positive individuals actually develop coeliac disease, so there must be a triggering environmental event. The objective of this project is to provide new knowledge of coeliac disease that can improve the diagnostics, the management, and possibly prevent the onset of this common disorder, using a large Norwegian population-based study, the Nord-Trøndelag Health Study (HUNT). All participants in the fourth HUNT study (HUNT4) will be screened for coeliac disease. As the disease might go clinically unrecognized for years, the true population-based prevalence and the rate of undiagnosed individuals with coeliac disease in the general population will be established. In this unselected population of individuals with coeliac disease, the consequences of the disease will be identified; including patient reported outcomes, symptoms, deficiencies, co-morbidity, based on data from HUNT and through linkage with local and national health registries. Using data, blood samples, and genotyping performed in the current and previous HUNT studies, new environmental triggering or modulating events and predictive factors will be identified, in addition to new and modifying genetic factors.

Publications from Cristin

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FRIMEDBIO-Fri prosj.st. med.,helse,biol

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