SilverbladeTE
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I'm looking at your source for that, and I'm not seeing anything about the 40x claim. Where are you getting that number from the paper?This TT mutation makes you 40 times more sensitive to organophosphates pesticides, so these pesticides will have a far, far stronger affect on people with the TT mutation, compared to those without this mutation. More info here.
I'm looking at your source for that, and I'm not seeing anything about the 40x claim. Where are you getting that number from the paper?
Note:There is a 10- to 40-fold inter individual difference in serum PON1 paraoxonase activity due, in part, to four common polymorphisms: functional promoter region polymorphisms include PON1C-108T and PON1G-162A, and the functional coding polymorphisms are PON1Q192R and PON1L55M.
Variations at these four common polymorphisms explain 44% of the phenylacetate and 88% of the paraoxon hydrolysis activity of PON1 in subjects without vascular disease and 25% of the phenylacetate and 82% of the paraoxon hydrolysis activity in subjects with severe carotid artery disease, with PON1192 largely accounting for the paraoxon hydrolysis variation.
Exposure to tri-o-cresyl phosphate detected in jet airplane passengers
The study concludes:
We propose a mechanism for tri-o-cresyl phosphate induced neurodegeneration in which low dose exposure to tri-o-cresyl phosphate causes disruption of axonal transport (Terry et al., 2007). The axonal transport disruption initiates irreversible degradation of neurons and loss of neuronal function.
Yeah, but according to the initial paper quoted, which does break things down by SNP ... rs662 TT is only reducing enzyme levels to about 40% of normal. So a bit less than half of normal, versus 1/40th of normal.
And it's impossible to extract the effect of a single SNP from a study only looking at the effect of the SNPs in combination. The combined effect certainly can't be imputed to a single member of the group.
I suppose Table II has the most relevant information. In the controls, "PON activity" for controls is 174.5 for QQ and 147.6 for RR. Assuming that "activity" does mean "activity" and not "levels", RR results in about 84.6% of the activity as QQ.Are you referring to the paper: Paraoxonase 1 (PON1) gene -108C>T and p.Q192R polymorphisms and aryl esterase activity of the enzyme in patients with dementia ?
Could you point out where it says that please.
Agreed, and it would be nice to see more data regarding this. Especially since some of the research that I glanced at suggests that there's a trade-off regarding that SNP, where one mutation is better at dealing with one toxin, and the other mutation is better at dealing with a different toxin.Note that PON1 blood enzyme levels are one aspect, and the efficiency of the PON1 enzyme at performing hydrolysis is another. As I understand it, the actual ability of the PON1 enzyme to detoxify organophosphate is determined by both enzyme blood levels and enzyme hydrolysis efficiency.
It probably is justified, but it's a very nonspecific claim to make. No absolute percentage of the gene function is being attributed to that mutation, so it's hard to make much of it, beyond "probably important, please do more research and get more data".Are you saying that the study quoted above which found "PON1192 largely accounting for the paraoxon hydrolysis variation" is not justified in concluding that?
Agreed, and it would be nice to see more data regarding this. Especially since some of the research that I glanced at suggests that there's a trade-off regarding that SNP, where one mutation is better at dealing with one toxin, and the other mutation is better at dealing with a different toxin.
Yeah, and exposing someone to organophosphates to see how their genotype impacts their ability to process it would be "ethically complicated"I am not sure if there is an easy way to directly measure PON1 activity in an individual via a blood test say. That would presumably be the most reliable way of gauging a person's detoxification ability for organophosphates.
For a group of people who think they have been affected by organophosphates and developed ill health conditions such as aerotoxic syndrome, it is possible that by genotype testing via 23andm3.com for their PON1 alleles, to find out how good the individuals in the group are at detoxifying organophosphates, this might offer proof that their illness was indeed caused by these organophosphates. This is because you would expect that on average, this group would have a much poorer than normal ability to detoxifying organophosphates, which is likely why they, but not other airline staff they work with, were affected.
In others words, in this affected group, you would expect to find a high prevalence of the TT allele of rs662, and a high prevalence of the other SNPs which lead to poorer detoxification ability. So if this group were tested by 23andm3.com and found to have a much higher prevalence of TT than you would normally expect to find by chance, then it I think it would offer some supporting proof that this group's ill health was indeed caused by their organophosphate exposure.
Do you have evidences that the PON1 is involved in cresyl-Phosphate detox process?
ToCP = tri-ortho-cresyl phosphate, which is a highly toxic isomer of tricresyl phosphate. It says here that concerns about tricresyl phosphate toxicity are largely based on the tri-ortho-cresyl phosphate isomer content, and the mono-ortho-cresyl phosphate isomer content. So it is detoxification of these ortho-cresyl phosphates that would be the main interest.Given the structural resemblance of ToCP with known organophosphate-substrates of paraoxonase 1 (PON1), PON1 is likely responsible for its detoxification.