KINESIOL 1Y03 Chapter 11: Gene-env interactions in IBD
22 Jun 2018
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Gene-environment interactions in IBD (see also genetics of IBD lecture for genetic bit)
Both Crohn’s and UC have increased in incidence rapidly since the 1950’s at a rate
implicating environmental factors (as this is too fast to be genetic selection)
MZ twin concordance = 35-60% in Crohn’s, 10-15% in UC
40-45% non-heritable influence in CD, and even greater environmental influence in
UC
Environmental factors
Smoking
RR of UC = 0.4 i.e. it is protective. This may be due to
-rectal blood flow
-mucus production
-nicotine may modify cytokines or eicosanoids
Patients who resume smoking notice improvement / remission
Nicotine patches shown to have some effect but doses required generally too high for
people to tolerate
RR of CD = 2 i.e. it is causative
Seen more in US than in eastern populations .g. Japan / India
Appendicectomy
Protective against UC (RR=0.3-0.7)
May also be associated with less severe course (lower colectomy rate and less
immunosuppressive use
However must happen before 19yo!
Less convinving data in CD but small reduction in risk
Gut flora = most important environmental factor
Implicated in murine models, as animals housed in germ-free environements do not get
colitis
Some colitis can be induced by different bacterial strains e.g. helicobacter
In humans, there is altered composition of gut flora in IBD patients:
Reduced flora variation
Increased populations of enterobacteracea
Increased enteroadhesive E.Coli
Reduced clostridia spp.
The gut flora in UC is different but overlapping to that in normals; in Crohns it is completely
different
-Chung, Cell, 2012 showed that gut flora can not be introduced, and rather it is genetically
determined. This illustrates that genes influence environmental factors
-Cadwell. Cell 2010 showed that ATLG16L1 transgenic (hypomorphic) mice have abnormal
Paneth cell function due to presence of gut flora, but colitis resolved in a clean environment
Found a murine norovirus (MNV) was required to affect gut flora, as well as the
polymorphism, to produce the colitis
Hence 1) polymorphism 2) environment 3) MNV was required for colitis
This shows how other factors can be required and how environmental factors can affect
genes
I.E THERE IS TWO-WAY INTERACTION, BETWEEN GENES AND ENVIRONMENT, AND
ENVIRONEMENT MODIFYING GENES
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Gene-environment interactions in ibd (see also genetics of ibd lecture for genetic bit) Both crohn"s and uc have increased in incidence rapidly since the 1950"s at a rate implicating environmental factors (as this is too fast to be genetic selection) Mz twin concordance = 35-60% in crohn"s, 10-15% in uc. 40-45% non-heritable influence in cd, and even greater environmental influence in. Rr of uc = 0. 4 i. e. it is protective. Patients who resume smoking notice improvement / remission. Nicotine patches shown to have some effect but doses required generally too high for people to tolerate. Rr of cd = 2 i. e. it is causative. Seen more in us than in eastern populations . g. May also be associated with less severe course (lower colectomy rate and less immunosuppressive use. Less convinving data in cd but small reduction in risk. Implicated in murine models, as animals housed in germ-free environements do not get colitis.
