GENE POOL

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. 

ACE and MAO
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.