VDR Genetics Part 1: Introduction

[Update Oct 2011: Since first writing this back in January new information has come to light. I no longer believe that VDR genetics have any significant effect on GcMAF-response (this is professor Yamamoto's position too). I believe other factors are far more significant - e.g. which coinfections a person has, whether their immune system is geared towards producing excessive inflammation, and the health of the HPA-axis]

There has been much confusion recently over the VDR (Vitamin D Receptor) tests which ME/CFS patients have taken in order to find out their potential response to GcMAF.

A paper by Ruggiero, Pacini & Yamamoto states that

"In fact, subjects harbouring homozygous “bb/FF” genotypes showed the highest response ... Heterozygous subjects (“Bb/Ff”) showed a smaller, but still significant, response, whereas “BB/ff” homozygous did not respond."

First a word on notation. An SNP (single-nucleotide polymorphism, pronounced "snip") is a part of a gene, e.g. the VDR gene, that varies from person to person. Fok1 and Bsm1 (hence shortened to Fok and Bsm respectively) are two SNPs of the VDR gene - i.e. two nucleotides that vary from person to person.

Normally in genetics, a capital letter denotes the "wild-type", dominant or non-mutated version of a SNP (e.g. "F" for the Fok SNP). The corresponding lower-case letter will then denote the mutated or recessive version of the SNP (e.g. "f" for Fok). However (as first pointed out to me by Joey Tuan), for Bsm the standard terminology is reversed. So bb refers to -/- (wild-type) and BB refers to +/+ (mutation).

[See Figure 2 from here for confirmation of the above: http://www.roche-applied-science.com/PROD_INF/BIOCHEMI/no3_05/pdf/p07.pdf]

Labs

The two main labs from which patients have tested are Amy Yasko's Holistic Health, and Red labs (who outsource testing to another unnamed lab).

Yasko's lab tests a range of genetics relating to methylation, Vitamin D, ACE etc. An example Yasko test can be seen here:

http://i1186.photobucket.com/albums/z380/John_Garcia/genetics.jpg

Red labs have a specific VDR genetics test where they test the two VDR SNPs Fok and Bsm.

Bsm = Taq (in most cases)

Yasko used to test the 3 VDR SNPs Fok, Bsm and Taq. However more recently they no longer test VDR Bsm, and instead only test VDR Taq. The reason for this is because they claim that VDR Bsm and Taq "track" each other for the vast majority of people, i.e. a mutation in one SNP corresponds to a mutation in another.

This claim is supported by the literature. I've been looking at a few VDR studies on population distributions of Taq & Bsm, and the numbers do seem to correlate (i.e. the numbers of tt would roughly equal BB, Tt would roughly equal Bb and TT would equal bb). The numbers alone don't tell us if the exact same people who have tt have BB etc. (we need joint distributions for that), but then I also found this study here:
http://www.springerlink.com/content/9hjra4g5wxd814tc/

which looks at 3 VDR snps: Apa, Bsm, and Taq. In particular they say:

The most common genotypes observed in our population were AaBbTt (37%), AABBtt (20%), aabbTT (15%), AabbTT (15%), and AABbTt (9%).

Ignore the Aa part since we are not interested in the Apa snp. But as you can see all of the above groups are people for whom Bsm and Taq are correlated (i.e. if BB then tt, if bb then TT, if Bb then Tt). Together that accounts for (37+20+15+15+9 =) 95% of the population. i.e. in that group of 120 people 95% had Bsm and Taq correlated.

Also from this paper here:

BsmI and TaqI genotypes were related in 89 of the 90 cases; hence, the same associations were found for both genotypes.

So it does seem that what Yasko is saying is true. Therefore people with a new style Yasko test can still deduce their Bsm status (by looking at Taq), albeit with slightly less than 100% certainty.

Why is this important?

Well we can directly compare the VDR genetics results given by the Yasko test with those given by Red labs.

Quite a few ME/CFS patients have tested using both labs and it appears that in every case so far Yasko's results for both Bsm and Fok are directly opposite to those of Red labs. For example if someone is +/+ for either Bsm or Fok by Yasko, they will show as -/- for that SNP by redlabs. Conversely if someone is -/- for either Bsm or Fok by Yasko, they will show as +/+ for that SNP by redlabs. Obviously heterozygous genotypes, +/- will show up as heterozygous on both tests.

In Part 2 of this discussion we will examine the Bsm SNP of the VDR.

In Part 3, we look at the Fok SNP.