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
Labels: MS genetics