Wednesday, 19 September 2012

Research: ApoE a different story today

Epidemiological studies have evaluated the association between Apolipoprotein E (ApoE) gene polymorphism and multiple sclerosis (MS) risk. However, the results remain conflicting. Therefore, in order to derive a more precise association of ApoE gene polymorphism with MS risk, we performed this meta-analysis. Systematic searches of electronic databases PubMed, Embase and Web of Science, as well as hand searching of the references of identified articles were performed. Twenty studies were identified, covering a total of 4,080 MS cases and 2,897 controls. The results showed evidence for significant association between ApoE ε2 mutation and MS risk (for ε2/ε4 versus ε3/ε3: OR=1.74, 95% CI=1.12-2.71, p=0.01; for ε2 allele versus ε3 allele: OR=1.16, 95% CI=1.01-1.35, p=0.04). In the subgroup analysis by ethnicity, the similar results were obtained among Europeans(for ε2/ε4 versus ε3/ε3: OR=1.81, 95% CI=1.14-2.87, p=0.01; for ε2 allele versus ε3 allele: OR=1.19, 95% CI=1.02-1.38, p=0.03). After excluding the outlier studies by observing Galbraith plot, marginal association was found between ApoE ε3/ε4 genotype and the protective factor for MS (for ε3/ε4 versus ε3/ε3: OR=0.86, 95% CI=0.75-0.99, p=0.04). In summary, the present meta-analysis provides evidence that ApoE ε2 mutation is associated with MS risk. In addition, ApoE ε3/ε4 genotype appears to be a protective factor for MS.
This study looks at other studies and suggests based on analysis of 5,000 MSers that there is an associated of Apolipoprotein E based on 20 small studies and suggests that the epsilon 2 variant is associated with MS risk and the epsilon3,epsilon 4 variants may be a protective factor. Now shoot back to a day ago and study of ApoE in over 20,000 MSers and found nothing.  So is it not surprising that MSers are confused by all this genetics stuff. I get confused too.

Well what do we believe? I think the single study rather than trying to cobble 5 studies is the better way to go and even in this study the odds ratio of risk of having an APO E variant is small is only 1.16 so the risk is small. (Odds ratio of 1 is no risk and 2 twice as likely). However even if the genetics does not find an association, it does not say that Apo E is not involved in the MS process. It could be critical but is not a variant in part of the disease pathway. For example one chain of the HLA-DR molecule is largely invariant and so every body has it, but when it combines with a certain beta chain it increase the risk to MS. However without HLA-DR there would not be the same immune response. Likewise genetic variants may have no influence on biological activity of the protein


  1. How does it matter to MSers which conclusions are correct? Why should we bother about these studies?

  2. If there is a variant that is linked to susceptibility then you have reason to believe that the protein is involved in the disease process. This then gives you an idea about inhibiting or augementing certain pathways that can be treatment avenues.


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