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Prevalence of genetic variants associated with inflammatory bowel disease in a healthy First Nations cohort.

ABSTRACT: Inflammatory bowel disease is the result of both genes and environment. Canadian First Nations people, despite living in a region with a high prevalence of inflammatory bowel disease, are relatively protected from this disease. We aimed to compare the carriage of genetic variants associated with inflammatory bowel disease in healthy First Nations and white people.DNA was extracted from the venous blood of healthy First Nations (n = 340) and white (n = 285) participants from Manitoba. Genotyping was performed for 69 single nucleotide polymorphisms (SNPs) with known or suspected associations with inflammatory bowel disease. We compared the genotypes between groups by logistic regression, adjusting for multiple testing. We calculated a risk score for the NOD2 gene by adding the number of risk alleles at three important NOD2 SNPs (G908R, R702W and 3020insC).We found genetic variation between white and First Nations participants at 45 of 69 SNPs. Notably, carriage of the ATG16L1 T300A mutation was lower in First Nations participants (p = 4.1 × 10(-30)). Cumulative carriage of important NOD2 variants was significantly lower among First Nations participants (3.9% v. 15.2%; p < 0.0001 for risk score) than among white participants. Risk variants in IL23R (p = 0.014) and IL12B (p = 1.2 × 10(-16)), among others, were more prevalent among First Nations participants than among white participants.The low prevalence of variants associated with bacterial processing and handling in First Nations people may explain their relative protection from inflammatory bowel disease. Increased carriage of a number of risk variants, for example in the interleukin-23/Th17 pathway, is especially intriguing given their importance in other inflammatory diseases of high incidence in First Nations populations.

SUBMITTER: Murdoch TB

PROVIDER: S-EPMC3348221 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Prevalence of genetic variants associated with inflammatory bowel disease in a healthy First Nations cohort.

Murdoch Travis B TB Bernstein Charles N CN El-Gabalawy Hani H Stempak Joanne M JM Sargent Michael M Elias Brenda B Xu Wei W Pathan Saad S Pathan Saad S Silverberg Mark S MS

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20120410 8

<h4>Background</h4>Inflammatory bowel disease is the result of both genes and environment. Canadian First Nations people, despite living in a region with a high prevalence of inflammatory bowel disease, are relatively protected from this disease. We aimed to compare the carriage of genetic variants associated with inflammatory bowel disease in healthy First Nations and white people.<h4>Methods</h4>DNA was extracted from the venous blood of healthy First Nations (n = 340) and white (n = 285) part ...[more]

PMID: 22496383

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Project description:BackgroundInflammatory bowel disease (IBD) has a significant impact on quality of life for many people.ObjectiveTo assess the prevalence of common mental health conditions in IBD and the combined impact of IBD and mental health conditions on healthcare use and time off work.MethodsA UK population-based primary care database (Royal College of General Practitioners Research and Surveillance Centre) was used to identify adults with IBD (n=19 011) (Crohn's disease (CD) or ulcerative colitis (UC)), and matched controls (n=76 044). Prevalences of anxiety, depressive episodes and depressive disorder recorded in primary care were assessed between 2016 and 2018. Outcomes comprised of rates of primary care visits, emergency secondary care visits, certificates for time off work, antidepressant and anxiolytic prescriptions.FindingsMental health conditions were more common in people with CD than controls: anxiety episodes (3.5% vs 3.0%; p=0.02), depressive episodes (5.7% vs 4.1%; p<0.001) and depressive disorder (17.5% vs 12.9%; p<0.001), and people with UC versus controls: depressive episodes (4.4% vs 3.6%; p<0.001) and depressive disorder (14.2% vs 12.4%; p<0.001). Healthcare utilisation rates were higher in people with IBD than controls (primary care visits incidence rate ratio 1.47 (95% CI 1.43 to 1.51); emergency secondary care visits 1.87 (1.79 to 1.95); fitness for work certificates 1.53 (1.44 to 1.62); antidepressant use 1.22 (1.13 to 1.32); anxiolytic use 1.20 (1.01 to 1.41)). In people with IBD, mental health conditions were associated with additional increases in healthcare use and time off work.ConclusionDepression and anxiety are more common in people with IBD than matched controls. Healthcare utilisation and prescribing of psychotropic medications are also higher in people with IBD. Mental health conditions in people with IBD are associated with additional healthcare use and time off work.Clinical implicationsEvidence-based mental health support programmes, including psychological treatments, are needed for people with IBD.

Dataset Information

Prevalence of genetic variants associated with inflammatory bowel disease in a healthy First Nations cohort.

Publications

Prevalence of genetic variants associated with inflammatory bowel disease in a healthy First Nations cohort.

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