VDR Genetics Part 2: Bsm

Mindy Kitei has recently posted 2 blogs regarding the discrepancy in testing for the Bsm SNP:

CFS Central: Gene Pool

CFS Central: Genes Redux

In particular she tentatively concludes (based on a statistical analysis) that Yasko's Bsm reporting of what is Wild-type (-/- or bb) and what is a mutation (+/+ or BB) are opposite to the standard reporting.

I can add to Mindy's evidence, by using two arguments.

1. Population Frequencies
According to Yasko's results BB is more common than bb in the ME/CFS population.

All the literature I have searched states bb is way more common than BB, in both the general population and disease groups.

For example in these 2 studies on the Japanese, the BB genotype is exceptionally rare (less than 1%):

1. http://ajrccm.atsjournals.org/cgi/content/full/160/4/1107
2. http://jcem.endojournals.org/cgi/content/full/88/7/3137/T1

It is possible that the Japanese may have unusual genetics though.

The following study, however, is on non-Hispanic white Americans:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938035/

In particular table 3 from that paper shows that BB has a frequency of 17.7% and bb 31.5%. This contrasts with Yasko's figures of 34% for BB and 14.9% for bb.

So in other words what Yasko calls -/- for Bsm is most likely in fact +/+ (and vice versa).

There is a potential flaw in the above frequency analysis in that it could be that the frequencies for the Bsm SNP are just so different in the ME/CFS population that the most common allele is reversed.

Indeed from the gene chart Mindy Kitei & W. L. Karns compiled, of 6 SNPs which differ with statistical significance from controls, 2 of them (COMT, MTRR) are so different that the most common allele in ME/CFS is reversed.

2. Call letters

As second more robust argument can be made by looking at the call letters for the + and - alleles for Bsm. On Yasko's test Bsm is +G/-A. In other words G represents a mutation or +, and A represents a wild-type allele or -.

However if we look at this HIV study here:

http://jid.oxfordjournals.org/content/197/3/405/F4.large.jpg

we can see from the figures for both HIV and controls that G is the common/wild-type allele and A is the mutation (GG is roughly twice as common as AA).

Conclusion

Yasko's lab seem to be reporting Bsm the opposite to the standard nomenclature. 
Red labs however seem to be reporting Bsm correctly.

Therefore the ideal Bsm genotype for GcMAF, namely bb, corresponds to +/+ on a Yasko test for Bsm/Taq.

That just leaves the Fok SNP which will be dealt with in Part 3.