Monday, January 10, 2011


The VDR Gene

On the patient forum Phoenix Rising, there’s been discussion recently about mutations in the Vitamin D Receptor (VDR) gene predicting patient response to the experimental drug GcMAF.  GcMAF (pronounced G C “MAF”) is believed to work on HIV, cancer and, now, ME/CFS.  These diseases turn off white cells called macrophages whose job is to ingest pathogens, and GcMAF presumably turns macrophages back on. (See YouTube video at the bottom of this post for more information on GcMAF.)

Kenny de Meirleir
Belgian physician Kenny de Meirleir has been using GcMAF, coupled with an old antiviral, the injectable Nexavir (formerly called Kutapressin), on ME/CFS patients and reports that 80 percent are improving. Derived from pig liver, Kutapressin was first used as an anti-inflammatory for skin conditions.  In the 1980s, when doctors began using Kutapressin to treat ME/CFS—the drug is particularly effective against herpes viruses—it acquired the moniker “mini Ampligen.”

Mutations versus wild type
The patients more likely to respond to the GcMAF/Nexavir cocktail appear to be those expressing the wild type (no mutations) in VDR “Fok” and a double mutation in VDR “Bsm/Taq,” an unusual combination. Those with the opposite profile—a double mutation in Fok and no mutations in Bsm/Taq (another unusual combination)—have reportedly not responded to the drug cocktail.

The health of those squarely in the middle, with single mutations in both Bsm/Taq and Fok—the most common combo in both ME/CFS patients and healthy controls—is also improving on GcMAF and Nexavir, according to de Meirleir, though not as dramatically as those with double mutations in Bsm/Taq and wild type in Fok.  One helpful blood marker for responders is an accompanying rise in Vitamin D levels, which can be depressed with patients with mutations in the receptor and in patients with ME/CFS.

It’s not clear how patients with other permutations of Fok and Bsm/Taq mutations have responded to GcMAF and Nexavir. 

SNPs from 49 ME/CFS patients
The technical term geneticists use for a mutation is SNP (pronounced SNIP), which stands for Single Nucleotide Polymorphism. The “Reference SNP” number is abbreviated “rs.”  Many SNPs have more than one rs, some have none, some are numerical, others have letters.  Why?  For no other reason that the fact that the rs numbers haven’t been standardized—as if things weren’t complicated enough. 

To simplify matters, autism specialist Dr. Amy Yasko and others use terms like “Fok” and “Bsm/Tak” instead of rs numbers when discussing certain mutations in the VDR gene.

The chart (see URL below this post) was compiled by W. L. Karns and me.  The 49 patients included in the chart all have been diagnosed with ME/CFS. Some of the initial patient data was compiled in 2009 by "Sue."  Patients’ names have been replaced with numbers to protect their privacy. Below the genetics of these 49 patients are the genetics of healthy populations from studies we found on Pubmed.  We included controls because we wanted to see how the distribution of mutations in ME/CFS patients compared with the general population.  

Black boxes
By statistical analysis, ME/CFS patients did not differ significantly from controls, mutationally speaking, in most cases.  (However, that doesn't mean that mutations can't cause problems, especially for those with chronic illnesses.)  There were six exceptions: ACE, one COMT SNP, one MTHFR SNP, one MTRR SNP, one AHCY SNP, and one BHMT SNP, where more ME/CFS patients sported genetic mutations than their healthy counterparts. The black boxes distinguish these six SNPs.  Amy Yasko’s lab tested most of the ME/CFS patients. (Some autistic children have parents with ME/CFS.)  The genetic testing company 23andMe tested the rest. 

Because ME/CFS genetics are complex and confusing—not to mention sorely incomplete—let me take you through one SNP:  the VDR Fok. (The VDR Fok SNP is known as the VDR “FUCK U” SNP in some weary circles.  Similarly, the MTHFR gene is sometimes referred to, unaffectionately, as the “MOTHER FUCKER” gene.)

Note that the two VDR SNPs are in pink.  (There are many more VDR SNPS that Yasko and de Meirleir’s laboratory, Redlabs, don’t test for.  23andMe, for instance reports on 80 VDR SNPs.) Below the word “VDR” on the chart are the different rs numbers, letters or names for the SNPs.  The “yes” directly underneath signifies that 23andMe tests for it. (The company tests for nearly 600,000 mutations but doesn’t test for all the SNPs Yasko tests for.)  Next are the results of 49 ME/CFS patients.  Those with -/- have no mutation in that SNP. Those with +/+ have a double mutation. +/- means there’s a single mutation. 

We compared the data from the 49 ME/CFS patients with the general population. The study source for that data is blank because Google Docs doesn’t allow for rich text of the Excel file from which this chart hails, and putting in the whole address would take up too much space. 

General population versus ME/CFS population
The percentages in white represent ME/CFS patients; in purple are the controls.  Also included in the chart are both the P value (P stands for probability) and the statistical method used to determine whether the mutation percentages are statistically significant.  In the case of the two VDR SNPs, it’s a chi-square distribution, and the ME/CFS population doesn’t differ significantly from the general population. Some of the other SNP stats were calculated through FET, which stands for Fisher’s Exact Test.

Blank spaces mean either the SNPS weren’t tested or there is no data. 

Here are some SNP exceptions: 
  • ACE, one of the few genes in which more patients than controls had mutations, isn’t really a mutation at all, but a deletion
  • The MAO gene resides on the X chromosome, so males, who have only one X chromosome (which they inherit from their mothers), have only one MAO SNP.  Females have two X chromosomes—one inherited from each parent—so they sport a pair of SNPs.  In the interest of simplicity, Amy Yasko lists males with a +/+ or a -/- for the MAO gene. In actuality, however, males have only one – or +.  23andMe uses the letter “T” to signify +. 
Genetic research is difficult because of the double whammy: So little is known, and so much of what is known is confusing.

To view W.L. Karns and Mindy Kitei's gene file, go here:  The Gene Chart

This article and the accompanying chart are copyright CFS Central 2010. All Rights Reserved. You may quote up to 150 words from this article as long as you indicate in the body of your post (as opposed to a footnote or an endnote) that the excerpt is by Mindy Kitei for CFS Central. You may not reprint the chart or more than 150 words from this article on blogs, forums, websites or any other online or print venue. Instead, refer readers to this blog to read the article and view the chart.


  1. Thank you for the very interesting article, which I'm still digesting.

    Pardon my rather naive question, which is only on one tiny part of this.

    I was recently diagnosed as Vit D deficient, and this got me thinking. My GP was spectacularly unworried by the result - he thinks as many as 1/3 of the population, if tested, would prove deficient.

    This article moots a mutation in the Vit D receptor gene as potentially an indicator of response to one treatment.

    But, would a mutation such as this mean there would be a noticeable difference either in tested Vit D levels for CFS patients or a patient's response to supplementation?


    Neurobiol Aging. 2009 Mar;30(3):466-73. Epub 2007 Aug 21.
    VDR gene variants associate with cognitive function and depressive symptoms in old age.

    Kuningas M, Mooijaart SP, Jolles J, Slagboom PE, Westendorp RG, van Heemst D.

    Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.

    Vitamin D has been recently implicated in brain function. Our objective was to test whether genetic variance in the vitamin D receptor (VDR) gene is associated with cognitive functioning and depressive symptoms in old age. The study was carried out in the prospective population-based Leiden 85-plus Study. All 563 participants of the study were genotyped for Cdx-2, FokI, BsmI, ApaI and TaqI polymorphisms in the VDR gene. Our data revealed an overall worse performance on tests measuring cognitive functioning for carriers of BsmI (p=0.013) and TaqI (p=0.004) polymorphisms, and of haplotype 2 (BAt) (p=0.004). In contrast, carriers of ApaI variant-allele and of haplotype 1 (baT) had better cognitive functioning together with less depressive symptoms. These associations could not be explained by differences in calcium levels, and by selective survival, since no associations between the VDR gene variants and calcium levels and mortality were observed. In conclusion, our results show that genetic variance in the VDR gene influences the susceptibility to age-related changes in cognitive functioning and in depressive symptoms.

  3. Many patients on GcMAF and Nexavir, de Meirleir has reported, experience an increase in their vitamin D levels. In fact, he has said that patients should not take vitamin D supplements while on the drugs, as their vitamin D levels may get too high. Too high of a level can be toxic.

    Interestingly, I know one patient on antiretroviral (ARV) drugs who has also experienced a sudden and dramatic rise in vitamin D levels. Previously, despite supplementation, her levels remained low and no amount of vitamin D resulted in her blood level increasing more than a point or two. After two months on ARVs, however, her vitamin D level had jumped 20 points.

    Anecdotal, yes, but interesting.

  4. Interesting that Vitamin D defeciency is seen in MS and schizoprenia as well...both which are neuroimmune based illnesses. Herve Perron from Geneuro and others think MSRV endogenous retrovirus is associated with these disorders and is interesting as well.For an article on the subject see: The Insanity Virus in June(or was it July) Discover magazine.

  5. hi,
    I had the yasko testing done a few years ago.
    here's a link to it if you were trying to look at the profiles of people with CFS that have had it done.

    SNP image:

  6. In the video, Nagalase is said to be an N-cutter, but two experiments seem to contradict that. One says there is plenty of Gc with all three sugars in the serum of cancer patients, so that can't be the reason in vivo creation of GcMAF is prevented. Another says that Nagalase mixed with GcMAF for many hours does not reduce the effectiveness of GcMAF created in vitro.

    What test is available to measure the Nagalase level in one's blood serum anyway?

    I want to know more about whether Nagalase interferes with the B-cell G cutter enzyme or with the T-cell N cutter enzyme. Note that the Nagalase stimulated by cancer and viruses is likely to be the kind that fetuses use to prevent activation of macrophages which would then attack the non-mom cells of the fetus.

    The other kind of Nagalase is used in all cells in the protein recycling centers called lysosomes and provides the low base-level of Nagalase in healthy, non-pregnant people. Contradictions invited.

  7. if a person does not have a rise in vit d levels while taking them it could also be celiac disease or gluten intolerance...a lot of cfs patients are not aware they are celiacs and also there are other factors involved to explain this...sincerely aidan walsh southampton, u.k.

  8. HI
    I had stopped all grains going on SCD to heal digestion and was always lo on vite D test(25OH), around 20. Evan if took 4000IS's /day.
    Wondered if using up or not absorbing, and how test for that. An aquantance said she had Lymes and that spiroquite uses the vite D for itself.Wonder if the body hides it like iron, too fight off infection?
    Sounds very complicated.
    Lynn D


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