Can you suggest (or write) a better article on MAO A gene polymorphism and treatments???
Last I checked there was extremely little useful web / blog info for the end user. People post and ask about this SNP literally every day.
I could write a better article but I don't have the energy nor the motivation to do the research about what recent robust GWAS have found about MAO A - ie what disease associations are likely to be real, nor about any recent robust studies of genetic linkage to MAO A protein activity and the consequence.
Nor could I comment about treatment since, as far as I know, there are only two well established polymorphisms with consequences - viz the promoter repeat polymorphism which I mentioned above, and the one which leads to Brunner syndrome. The former appears to mediate a complex interaction between environment and gene to exert an effect, while the latter, in which a truncated non-functional protein is produced, results in aggressive behaviour and mental retardation in males.
I am not qualified to comment about treatment for such complex conditions.
I can make some general comments about MAO A SNPs and some of the inadequacies in the Cohen article.
First I would draw peoples attention to the OMIM
entry which explains that only the two MAO A variants I noted above have been robustly shown to be pathogenic.
Then I would point out that R297R doesn't need treating.
The people asking about treatment for this SNP have been mislead by the claims by Yasko, endlessly repeated on the internet with no basis whatsoever. They have fallen for the notion that because a variant is identified, something must be done about it. This may sell supplements but it has no basis in reality.
I would explain that this variant doesn't do anything. The name gives it away. The arginine (abbreviated as R) at position 297 in the protein remains as arginine. This variant does NOT produce a slow form of the enzyme as is claimed, it produces a protein identical to the one produced by the ancestral gene.
I would go into explanations about other possible reasons for such a synonymous variant exerting an effect. For example the nucleotide change could lead to an unstable mRNA which could result in less protein being produced (NOT a slower form of the protein). This has been described for some SNPs but not in isolation. Usually it is the presence of several such SNPs close together in the secondary structure which destabilised the mRNA.
There is no evidence that this applies to this SNP so I can find no basis for Cohen's claim that this variant produces less enzyme, nor does he give any reference for the claim.
Alternatively the SNP could be acting as a proxy for something else and the latter is really exerting the effect. I did once try to chase down this possibility but I came up with nothing.
I would explain that R297R is not the warrior gene by first explaining about the repeat motif in the promoter that does define this gene, as in my earlier post. Cohen doesn't explain this at all and one is left wondering what 2R, 3R etc refer to. Furthermore I would emphasise that an environmental interaction was necessary for the low repeat variant to exert its effect. There appears to be an epigenetic component.
Regarding Cohen's discussion of SNPs which are proxies for the promoter repeats, I have read the references he linked. Although he appears to give a lot of references actually most of them are for a single article - there are only two references.
These don't say what he says they say. The one which he uses over and over again is actually just an association study between various SNPs and anger expression in suicide vs non-suicide attemptors and in succeeders. It has nothing to do with the promoter polymorphism. It is a very small study, much too small to be definitive.
The other study is interesting, a bit complicated, trying to look at epigentic and genetic factors involved in mRNA expression. It does define some haplotypes which include the promoter repeat but it most definitely does not say the the three SNPs he lists define the 5R version.
He gives no reference for his opening statement that rs909525 is the best proxy for the number of repeats in the promoter. I looked at the references linked by dsSNP to this SNP and can't find anything and I don't have the energy or the interest to follow this up further. Even if we take Cohen at face value it is only an association, something that is more likely. Association studies are notoriously poor so I would definitely need to see this study before I gave it any credence, but as I said I can't find it.
At this point in the article I pretty much gave up. I thought his evidence was poor and his explanations were either wrong, dubious or incomprehensible.
