Crohn's Disease and Ulcerative Colitis...What are they?
Both of them are forms of IBD and happen to be idiopathic (unknown cause), with speculations lying in genetics and environmental factors. According to a review article by Baumgart and Carding, lots of research has pointed in genetics being a major contributing factor, with Ashkenazi Jews having an 8 times increased risk compared to other ethnic groups. Genetics only point at this trend but does not specifically answer why this trend exists. More than a dozen mutated regions on our chromosomes have pointed to IBD, and with the variation, everybody is affected by IBD differently. One gene that this review paper talks about in particular is the CARD15 (NOD2) gene. This gene codes for the NOD2 protein, a intracellular pattern-recognition receptor. With a mutation, it results "in a disturbance in the normal immunological unresponsiveness of the mucosal immune system to components of the commensal intestinal microbiota." In short, the NOD2 recognizes the good things in our intestines as bad, and creates an inflammatory response.
In the United States alone, the risk is higher for white and African-American individuals. Most of IBD also has a higher occurence in more developed countries. Epidemiological differences are seen in people of the same ethnicities, living in different locations. Researchers have looked into things we can change in order to alleviate the symptoms of IBD. Lifestyle changes like breastfeeding, dietary consumption, and smoking have been hypothesized to help.
What I find most interesting is the fact that environmental factors even has any effect at all on this disease. Is it our lifestyle that causes these mutations, and if so, there seems to be some simple life altering choices we can make that would diminish the effects of IBD.
After going through this paper, I too was curious as to why environmntal factors would play a significant role whatsoever in this disease. The paper mentioned that prevalence of both types of diseases are seen in especially in the UK, northern Europe, and North America and also that both diseases are seen more in Jewish people. The claim that it is significantly more prevalent in a certain ethnicity made me curious as to why. After a little research I tried to find the most recent posed explanations. From my understanding, many research results claim that it's more so due to geographic/environmental factors as you mentioned, but I was wondering if you though maybe the genetic lineage of Jewish families was a possible risk factor for acquiring both Crohn's and Ulcerative colitis?
ReplyDeleteThis is the link to the paper that I found most helpful:
http://www.uptodate.com/contents/definition-epidemiology-and-risk-factors-in-inflammatory-bowel-disease#H531113309
I also have been curious on why the Ashkenazi Jew is more prone to CD. I read that it's caused by the chromosomal defect on chromosome 16, called CARD15, that you also mentioned. But I can't seem to find specific environmental factors that could possibly cause this. What isit about their environment?
ReplyDeleteI haven't really found much explanation but I'm going to keep researching.
ReplyDeleteI was wondering the same thing as Yvette; what is it about certain environmental changes that makes them factors of IBD? Also, I read an article on Crohn's Disease on the US News Health column recently, and discovered that CD used to be less prevalent among African Americans than white Americans, but now the rates are pretty similar. This made me think that although genetics plays an important role in the development of CD, environmental changes are just as worthy of observation. The first explanation I could think of is that African Americans have become more sanitary over the years, and according to the hygiene hypothesis, the increasing amount of sanitation has made them more prone to diseases like CD. However, I also read that in the US, CD is less prevalent in the Latino, Native American, and Asian American populations. This might be me generalizing too much, but most Asian lifestyles and cultures stress the importance of sanitation, so if I were to follow the hygiene hypothesis, I would have expected CD to be more frequent in Asian American populations. But then, there's also genetic factors to take into account. So, I definitely understand why IBD is such a complex area of study and why researchers are still discovering which factors are more key. It would be really interesting to see how genetic and environmental factors work together to play a role in the development of CD and UC.
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ReplyDeletePreviously, more than 25 recessive disease founder alleles have been found to afflict Ashkenazi populations, Crohn’s disease being one of them. I was also curious as to why Askenazi Jews are at an increased risk of acquiring IBD. Most of the articles I read were popular periodicals like sciencedaily.com that only stated that this population was at increased risk, but didn’t really go into more depth as to why that is. Then I came across an article that I found on the Public Library of Science (PLOS) that discussed a large study that was done in order to understand Crohn's diseases-related genetic variants specific to the Ashkenazi Jewish population. The involvement of known Crohn’s disease risk variants were confirmed in this study such as RPL7, CPAMD8, PRG2, and PRG3, but genetic regions that were not previously found in non-Jewish European populations were also identified. While this study did provide some significant results, there is a limitation to this study. They said that this was study conducted on an isolated population, which affected the availability of the samples. In addition, they wondered if the results would have been different if a more outbred population was used. They think their study might have also overlooked joint disease loci because many of the controls were detected for other several complex disorders as well.
Those that conducted the study also felt that is possible that different gene-environment interactions could account for the distinct genetic loci that were identified in the study. While this study did assemble the largest sample of Crohn’s disease patients of Ashkenazi descent to date, there is still a need for further study in order to find the answers to remaining questions. I thought it was a pretty helpful article that helped me understand a little more about the genetics of this population. Here’s the link to the article:
http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002559
Colin brings up a good point because for a hereditary disease, it's hard to say if the environment even has an effect. In general, the Jewish population are more at risk for IBD but it would be really interesting to see how many of the cases are hereditary and how many, where the person is the first in their family to be afflicted by IBD.
ReplyDeleteMaybe it was just something about the environment where the majority of the Jewish population resided in the past...something causing their genetic mutations? I mean, for us in today's society, we hear things like UV radiation causing genetic mutations. In this case, it affects the hotter states like AZ, and then that all leads to skin cancer and such.
And response to Angela and Yvette, there are just so many factors that can contribute to IBD, like the review article talked about. The degree of sanitation in more developed countries is a factor but it's very hard for us to pinpoint one cause; there are just so many other contributing factors to a person's environment/location!
One of the lifestyle factors mentioned in your paper that I found really interesting was the fact that breastfeeding can provide protection against ulcerative colitis and Crohn's disease. I found several articles that supported this claim as well. Breast milk contains many antibodies and immune-protective substances which allow breast-fed babies to be at lower risk for many different ailments.
ReplyDeleteAn infant's nutrient intake is thought to play a major role in the development of a baby's GI tract. Nutrition regulates GI barrier function, gut motility, immunity of the mucosal layer, ability to absorb and digest, and microbe activity.
It was found that the genes activated as a newborn's GI tract develops are very different between breast-fed and formula-fed babies. Human milk contains hundreds of different oligosaccharides which interact directly with intestinal epithelial cells and can affect gene expression. Several lipids in human breast milk can also regulate gene activation. The protective components in breast milk are not found in formula, and this may play a role in our understanding of why formula is not protective against IBD.
http://ajpgi.physiology.org/content/298/5/G582.full.pdf+html
I like this point that KellyK has brought up. I know that I mainly talked about genetic mutations, like the CARD15 gene and such, and it's negative effects. For the most part, whenever you have a genetic mutation, it messes up how your body normally should function.
ReplyDeleteBut with Kelly's article on breastfeeding, I'm seeing another aspect, more specifically with epigenetics. This idea that there are different phenotypic expressions, but with various factors that turn on/off certain genes. This is different from genetic mutations because there is actually no direct change to the DNA sequence itself.
Maybe that's what some lifestyle changes are doing?? Turning off the bad genetic mutations in IBD patients?
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