Common Genes Found In Celiac And Crohn's Disease

ABSTRACT:
Crohn's disease (CD) and celiac disease (CelD) are chronic intestinal inflammatory diseases, involving genetic and environmental factors in their pathogenesis. The two diseases can co-occur within families, and studies suggest that CelD patients have a higher risk to develop CD than the general population. These observations suggest that CD and CelD may share common genetic risk loci. Two such shared loci, IL18RAP and PTPN2, have already been identified independently in these two diseases. The aim of our study was to explicitly identify shared risk loci for these diseases by combining results from genome-wide association study (GWAS) datasets of CD and CelD. Specifically, GWAS results from CelD (768 cases, 1,422 controls) and CD (3,230 cases, 4,829 controls) were combined in a meta-analysis. Nine independent regions had nominal association p-value <1.0×10−5 in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value <1×10−2 in CelD and <1×10−3 in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37×10−8 and 6.39×10−9, respectively, in the meta-analysis. The other seven had not been reported as shared loci and thus were tested in additional CelD (3,149 cases and 4,714 controls) and CD (1,835 cases and 1,669 controls) cohorts. Two of these loci, TAGAP and PUS10, showed significant evidence of replication (Bonferroni corrected p-values <0.0071) in the combined CelD and CD replication cohorts and were firmly established as shared risk loci of genome-wide significance, with overall combined p-values of 1.55×10−10 and 1.38×10−11 respectively. Through a meta-analysis of GWAS data from CD and CelD, we have identified four shared risk loci: PTPN2, IL18RAP, TAGAP, and PUS10. The combined analysis of the two datasets provided the power, lacking in the individual GWAS for single diseases, to detect shared loci with a relatively small effect.

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Gluten Sensitivity and the Brain-Is there a link?

The parents of a 9-year-old girl called Karen brought their worries to Dr David Perlmutter, a certified neurologist, describing her symptoms as a difficulty in thinking and focussing. They stated that at times she seemed fine, whilst at other times her brain function was clearly different. Because of her problems her parents decided to home school her, and Karen was several grades behind the level normal for a nine year old. Karen was in good health, with no significant medical problems in the past or present, but what caught the doctor’s attention was the fact that her problems were not constant, suggesting that the key to her symptoms may have lain in her diet.

Subsequent blood tests showed that Karen had a profound sensitivity to gluten, and after being put on a gluten-free diet her problems disappeared, allowing her to regain her fallen grades in leaps and bounds.

The link between gluten and the brain is becoming better known, and Dr Maios Hadjivassiliou has written in a report published in The Lancet, that ‘gluten sensitivity can be primarily and at times, exclusively a neurological disease’, meaning that some people with gluten sensitivity can have issues with brain function without any gastrointestinal problems at all. Gluten sensitivity is caused by elevated levels of antibodies against a component of gluten called gliadin. When the antibodies combine with gliadin, specific genes in a specific type of immune cell in the body are turned on, and it is these immune cells which create the cytokines which have such a devastating impact on the brain. This is because the brain does not like inflammation and responds negatively to the presence of cytokines. Elevated cytokine levels are seen in people with Alzheiner’s and Parkinson’s disease, autism and multiple sclerosis.

One percent of Americans (3 million people) are gluten sensitive, and of that number, 230,000 are children. Despite being so widespread, gluten sensitivity is still relatively obscure.


Source: Huffington Post