23andme - question about PON1 gene rs662

[globalpilot]

I wonder if someone can help me with this.

I'm looking at rs662 which corresponds to PON1 192 gene.
The normal variant of this gene codes for arginine and the variant (slower version) codes for glutamine.
http://www.ncbi.nlm.nih.gov/pubmed/12625227

My data shows that I am TT which means I have thymine in both locations. How do I know if the T codes for glutamine or arginine ?

Thanks for any help
GP

 

[snowathlete]

No idea, but i am CT whatever that means.

 

[nanonug]

I'm looking at rs662 which corresponds to PON1 192 gene. My data shows that I am TT which means I have thymine in both locations.

According to SNPedia, G (or C) is the risk allele. You are good to go!

By the way, I am GG!

 

[snowathlete]

so what does that mean for you and me nanonug?

 

[nanonug]

so what does that mean for you and me nanonug?

Probably increased oxidative stress, with all the bad things associated. Wikipedia has info about PON1. The G allele reduces its catalytic efficiency. It is one of the worse traits I have found so far for me.

 

[globalpilot]

Well this is strange. The link I provided says glutamine is the slower version. And SNPpedia says glutamine is the normal version. Do you see what I mean ?

FWIW, my paraoxonase was very low at 121 (normal 150-1000)

 

[nanonug]

Well this is strange. The link I provided says glutamine is the slower version. And SNPpedia says glutamine is the normal version. Do you see what I mean?

Well, it appears that things are a bit more complicated than it would seem just by looking at the article you posted or SNPedia. According to omim, "The arg192 isoform of paraoxonase hydrolyzes paraoxon more rapidly than the gln192 isoform. However, with respect to hydrolysis of toxic nerve agents, such as sarin, the arg192 isoform displays a lower activity than the other isoform". Allele 'A' codes for glutamine and 'G' codes for arginine. It appears that snowathlete is the lucky one!

FWIW, my paraoxonase was very low at 121 (normal 150-1000)

Not exactly sure what that might mean but I found this article:

"High plasma C-reactive protein (CRP) is related to low paraoxonase-I (PON-I) activity independently of high leptin and low adiponectin in type 2 diabetes mellitus."

By the way, how did you get your paraoxonase levels measured?

 

[globalpilot]

Ok, so it looks like my allele ("T") must code for arginine meaning I hydrolyze paraoxonase slower than those with the glen isoform. On another publication it was found to be 6 times slower.

- deepblue.lib.umich.edu/bitstream/2027.../210_2003_Article_833.pdf

I had the paraoxonase tested at biolab in the UK. The reason I did thi sis because my mother has atherosclerosis and it seemed to be unusally severe at a relatively young age. This enzyme has been linked to atherosclerosis.

 

[nanonug]

Ok, so it looks like my allele ("T") must code for arginine meaning I hydrolyze paraoxonase slower than those with the glen isoform. On another publication it was found to be 6 times slower. [...] This enzyme has been linked to atherosclerosis.

Table 1 on the "Pharmacogenetics of paraoxonases: a brief review" document for which you provided the link pretty much shows the trade-off between the two different alleles. However, this doesn't explain the low levels of the enzyme. Something must be inhibiting the expression of the corresponding gene in your case, no?

 

[globalpilot]

Is Vmax the correct measurement ? If so, it looks like it is .47 for the Q and 2.1 for the R for paraoxon hydrolysis. The Q is quite a bit lower. But, yes, mine is lower than the measurement of 150-1000 IU/L which takes into account all alleles including mine, so there is something additional going on.
Some additional reading revealed that infections and inflammation can lower it - maybe my gut dysbiosis is lowering mine. Also, d iabetics have lower amounts and the assumption is that there is a circulating factor.
I don' know how much of my low value is genetic and how much is acquired and I'm not sure this could be sorted out. Professor Paul Shattock has studied this and he 'strongly suspects' DMPS chelates the organophosphate metabolites paraoxonase normally detoxifies.

Table 1 on the "Pharmacogenetics of paraoxonases: a brief review" document for which you provided the link pretty much shows the trade-off between the two different alleles. However, this doesn't explain the low levels of the enzyme. Something must be inhibiting the expression of the corresponding gene in your case, no?

 

[nanonug]

Some additional reading revealed that infections and inflammation can lower it

That could be it. Do you know your C-reactive protein level? Should be elevated in inflamation.

By the way, according to omim, rs854560 is associated with serum concentrations. I don't have it on my 23andme V3 chip, though.

 

[globalpilot]

I've had it measured several times. It is generally within normal but occasionally high when I used to get Utis. I don't know what it was when I had the paroxonase measured. I"m thinking of measuring it (the paroxonase) again now that i've improved soemwhat. I really should be in range since the reported normal range covers all alleles.

rs854560 is the 55 ? Yes, I noticed they don't report that one. Too bad.

That could be it. Do you know your C-reactive protein level? Should be elevated in inflamation.

By the way, according to omim, rs854560 is associated with serum concentrations. I don't have it on my 23andme V3 chip, though.

 

[richvank]

Hi, nanonug and globalpilot.

At the IACFS/ME conference in Ottawa last September, Lea Steele presented a study on Gulf War veterans in which she correlated their PON1 genotypes to their vulnerability alternatively to sarin or to organophosphate pesticides and pyridostigmine bromide, which was given to the troops as a prophylactic in case of exposure to nerve gas. She found a significant correlation.

Best regards,

Rich

 

[globalpilot]

Thanks Rich. Is there a summary of her presentation somewhere ?

Hi, nanonug and globalpilot.

At the IACFS/ME conference in Ottawa last September, Lea Steele presented a study on Gulf War veterans in which she correlated their PON1 genotypes to their vulnerability alternatively to sarin or to organophosphate pesticides and pyridostigmine bromide, which was given to the troops as a prophylactic in case of exposure to nerve gas. She found a significant correlation.

Best regards,

Rich

 

[richvank]

Hi, globalpilot.

There's a hard copy syllabus with printed abstracts. I don't see it available on-line, though. I have a copy, and I'll type her conclusions section:

"Conclusions:

"Findings support earlier indicators that GWI may be associated with PON1 genotype and activity levels, with GW PON1 192RR homozygotes at somewhat increased risk for GWI overall. Detailed investigations from our small sample provided significant results in support of the following hypotheses: 1) GW veterans whose PON1 genotype (QQ) is known to provide slower hydrolysis of some organophosphate pesticides were at increased risk for GWI in relation to reported use of pesticides and prolonged use of pyridostigmine bromide during deployment, and 2) GW veterans who carry the R allele at PON1 192, which is known to provide inefficient hydrolysis of sarin, were at increased GWI risk if they heard chemical alarms in theater. These preliminary findings identify significant gene-exposure interactions in the directions expected for substrates preferentially hydrolyzed by PON1 192Q and R isozymes, and warrant further evaluation in a larger sample."

Lea Steele is at Baylor University, and her email address is Lea_Steele at baylor dot edu.

Best regards,

Rich

 

[nanonug]

Is there a summary of her presentation somewhere ?

I was able to find a document entitled "IACFS/ME Biennial International Conference - Abstracts from General Session". It contains the abstract richvank posted. But there are lots of other goodies there, too.

 

[snowathlete]

It appears that snowathlete is the lucky one!

YEAH BABY, COME ON!!!
I WON!!!

Las thing i won was a loaf of bread at a school harvest festival when i was about 6. SCORE!!!

 

[hixxy]

Did you manage to settle on what the risk allele is for PON1? It seems like it's different for different diseases .. I'm CC!

 

[nanonug]

Did you manage to settle on what the risk allele is for PON1? It seems like it's different for different diseases .. I'm CC!

I think both are bad in different ways. It's a "choice" between having problems due to atherosclerosis or pesticide exposure.

 

[hixxy]

What's the risk allele for pesticide exposure?