Research: ApoE a different story today

Yin YW, Zhang YD, Wang JZ, Li BH, Yang QW, Fang CQ, Gao CY, Li JC, Zhang LL. Association between apolipoprotein E gene polymorphism and the risk of multiple sclerosis: A meta-analysis of 6977 subjects. Gene. 2012 Sep 13. pii: S0378-1119(12)01091-8. doi: 10.1016/j.gene.2012.09.010. [Epub ahead of print]

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

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