Inflammatory bowel disease: dysfunction of autophagy?

[Crohn2357]

Inflammatory bowel disease: dysfunction of autophagy?
http://www.ncbi.nlm.nih.gov/pubmed/23295687

 

[wildbill_52280]

My thinking so far about these genes related to autophagy and the contribution of defective autophagy with intercellular pathogenic bacteria like MAP or Adherent Invasive Escherichia Coli(AIEC), is that supposedly the intestinal microbiota never should come into contact with the cell surface of the intestine in normal circumstances, so something must happen before a pathogen ever gets inside a cell to exploit some genetic weakness.

So at the moment, I dont think genetic variation is a major variable and something else is more important determinant as to who develops crohn's disease. I still believe it is a the disrupted intestinal microbiota, specifically, extinct bacteria that precedes and determines everything. A pathogen must get past the microbiota before it ever enters a cell.

Just like Nod2 variants cannot predict who develops crohn's and many people have nod2 variations and are perfectly healthy, it seems that the case may be that your genes only determine who gets worse forms of crohn's disease. At least this is what the current scientific evidence seems to suggest.

Using GWAS(Genome Wide Association Study) to Estimate Disease Risk
The practicality of identifying a correlation between a genetic change and the incidence of a complex disease is limited to statistical estimation of increased risk for developing the disorder, rather than a hard-and-fast prediction. This is due to the significant number of genetic and environmental variables that interact to cause the onset of a complex disease. Therefore, any genetic variant, such as a SNP(Single Nucleotide Polymorphim), makes only a small contribution to an individual's overall risk.

SOURCE:http://www.nature.com/scitable/topicpage/genetic-variation-and-disease-gwas-682