Debunking the cholinergic hypothesis of Gulf War Illness?

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I have Gulf War Illness. Or rather, whatever we’re calling the same symptoms in veterans of the war in Afghanistan. (The VA is currently calling them “chronic multisymptom illness” and “undiagnosed illnesses” because they don’t like the term “Gulf War Illness”).

This article repeated one of the more popular hypotheses about the cause of Gulf War Illness, that it is caused by cholinergic dysfunction due to exposure to organophosphates (pesticides, i.e. nerve agents) used by our own military on its members to keep nasty bugs away from us. (And in the process giving between a quarter and a third of us lifelong disabling symptoms of ME/CFS + Fibromyalgia. Thanks for keeping those mosquitoes away from me! 🙄)

Recently, I underwent RNA genotyping in order to determine which variant of the rs17228616 allele I possess:  the most common G;G variant, the less common G;T variant (occurring in about one-quarter of the population), or the extremely rare T;T variant. It was hypothesized that “[b]ecause rs17228616 promotes higher acetylcholinestase activity, [possessing the G;G variant] may be relatively protective against nerve agent and pyridostimine bromide exposure.” Naturally, I paid for this advanced genetic testing out of my own pocket, because it’s not “medically necessary” yet–it’s the stuff of pure research. But medicine moves too slow for me, so into the realm of research I have progressed.

I just got my results back and guess which rs17228616 allele I possess?  G;G. 😲

So, I’m not sure exactly what to make of this, except that consistent with various genetic tests I’ve had done on my DNA, I don’t seem to have been predisposed in any biological way to contract Gulf War Illness in Afghanistan. I’m just one of the unlucky one-quarter to one-third of war veterans who got sick from…something…we were exposed to over there.

On a more positive note, this article suggests repairing microtubules damaged by something might reverse some or all of the symptoms of Gulf War Illness. Let’s work on reversing that brain damage, please! Additionally, this article involved testing gene expression in Gulf War Illness patients and comparing it to other diseases, finding the highest level of gene expression overlap with Rheumatoid Arthritis and hypothesizing that the following medications might relieve some or all of Gulf War Illness’s symptoms: Infliximab, Adalimumab, Etanercept, Leflunomide, Cispatin, Tamoxifen, and Fulvestrant. Needless to say, I am pursuing a medication trial with one of those seven listed glimmers of hope, as I have no intention of quietly sitting (or lying down) and continuing to waste away!

So what did I learn? That the hypothesized “minor RNA allele leaving me more susceptible to neurological damage from pesticide exposure,” or in other words, that I was genetically predisposed to get Gulf War Illness, is apparently not true, at least in my case. I have the “healthiest” genetic variant of rs17228616 and should have had the highest level of protection against pesticide exposure causing permanent neurological damage going into my deployment to Afghanistan. I still got sick, and am still permanently disabled barring a major medical breakthrough in the treatment of either Gulf War Illness or ME/CFS. (Which may or may not be the same disease, in spite of having the same symptoms). On the positive side, as previous DNA testing has shown, I have “great genes” that present a low risk of various health problems, so at least I passed “healthy” genetic material on to my children.

I think there is far more to this medical mystery left to uncover… 🤔

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