SNPs Potentially related to CIS

I have found experimentally that I seem to be sensitive to cholinesterase inhibitors (CIS) at levels typically encountered in the food supply unless actively avoided. I found that 23andMe could test for some of the single nucleotide polymorphisms (SNPs) in genes relevant to CIS. This is an attempt to try to see if the 23andMe results can shed any light on which potential causes of CIS in my case may or may not be useful to pursue.

The SNPs most likely to be relevant are now reflected on SNPedia at http://www.snpedia.com/index.php/Cholinesterase_Inhibitors and results will appear in future Promethease reports under Topics/Cholinesterase Inhibitors. Thanks go to Mike Cariaso for making this happen.

The results for the SNPs I had found in the literature on cholinesterase inhibitors, reflected in the first table, were not as dramatic as I had hoped:

• • BCHE = heterozygous for decreased BuChE activity

  • I don't have the uncommon version of any of the three BCHE SNPs that I can successfully cross reference between Dr. Soreq's work and the 23andMe results. I am, however, heterozygous for the "BCHE K variant." According to omim, this variant decreases BuChE activity by 33%. Based on this, the versions of BCHE I have are somewhat less effective than most people's as a defense against cholinesterase inhibitors (CIs). This doesn't seem enough by itself to explain CIS, but it could contribute.

  • PON1 = heterozygous for decreased catalytic efficiency

  • That implies that one copy of my PON1 gene yields PON enzymes which are not as useful as they could be for breaking down certain CI pesticides. This also doesn't seem enough by itself to explain CIS, but it could contribute. It's not clear whether or not it helps explain sensitivity to nightshades. I can't find any evidence that PON is involved in breaking down solanaceous glycoalkaloids (SGA). On the other hand, I can't find any evidence that anyone has studied the mechanism for breaking down SGA, so PON is as likely as anything else at this point. Hopefully one day I'll find the answer to this one.

The other polymorphisms Dr. Soreq's group has found to affect CI response are either SNPs which 23andme does not test for, or I can't figure out the mapping, or they are not SNPs (some are deletions or insertions). Unfortunately I have not yet found another way short of full genome sequencing to check for them.

On the plus side, the 23andme/Promethease results did also turn up some other directions to pursue which I would not have thought of. These were atypical results for receptors potentially relevant to neurochemicals affected by CI levels. They would not affect the breakdown or prevalence of CIs, but they may affect the likelihood of noticing physiological consequences related to CI levels. These are reflected in the second table.

The third table is a complete shot in the dark. It explores the question of whether any of the other SNP results 23andme tests for in the BCHE and PON1 genes were particularly atypical, without having any idea of whether or not those changes are relevant to function.

SNPs known to affect genes relevant to CIS

Atypical SNPs from 23andMe that might relate to CIS

SNPs 23andMe reports for relevant enzymes, but unknown impact

Homozygous for uncommon allele marked in red, heterozygous < 25% incidence in yellow.