I got this from Yasko's forum. Seems she's changing things around because of the controversy over things? If this isn't typical Yasko I don't know what is. A huge, complicated answer that still really doesn't give you an answer. Dr. Vank, can you make heads or tails of this? I have a friend who got her results last month and has no idea if its + or - or whats what? It would help if she'd just say she doesn't have all the answers but for now, we can read this as positive or that as negative. Thank you, Angela VDR information: Recently there has been a barrage of questions related to VDR. The situation with respect to VDR is highly complex which is why I have not tried to thoroughly explain it in the past. I have tried to keep it simple for you and note the observed clinical relationship between those who cannot tolerate higher levels of methyl donors (tt) and those that can handle more methyl donors (TT) in terms of their Taq status. Based on the volume of questions and confusion regarding VDR I will go ahead and explain the complexity of the situation. I believe this recent flurry of interest in the genotype designations for the VDR is related to of the use of GcMAF. While initially it was thought that the VDR SNP data played a role in determining the use of that agent, it has since been suggested that simply the use of Vitamin D may be a help. As such this focus on VDR may not be necessary. I had reached a similar conclusion with regard to vitamin D for my program a while ago with the additional caveat that I feel support for the receptors is also important. The bottom line is that I do feel vitamin D support is a positive, and the use of rosemary, sage and resveratrol can also help support healthy vitamin D levels. First a quick point of nomenclature before I go in to the complexity of the situation. In general the presence of the restriction site is denoted by a lower case letter and the polymorphism that eliminates the site is denoted by an upper case letter. The situation is more complex in that the Bsm and Taq sites have an inverse relationship. To add to the confusion, studies have found decreased levels of VDR protein with Bsm BB and Taq tt genotypes compared to other genotypes yet vitamin D levels were significantly increased at the same time that levels of VDR protein were significantly decreased. Thus increased 1,25(OH)2 D3 levels, might lead to downregulation of VDR expression. Decreased VDR levels could result in defective VDR signaling.( JOURNAL CLINICAL IMMUNOLOGY Volume 29, Number 4 (2009), 470-478 ) The situation with Fok is also complex as the polymorphism (FF, loss of site) actually leads to the production of a protein with increased activity. The Fok SNP, situated in exon 2, gives rise to an alteration in the start codon position resulting in a 3 amino acid longer protein produced by the F allele. So the Fok site affects the protein directly such that those who are missing the restriction site (FF) make a shorter protein, but one that is actually more active. While those who do not have a ‘mutation’ and have the restriction site actually make the full length protein but it has less activity.(Nutrition Reviews, What Are the Frequency, Distribution, and Functional Effects of Vitamin D Receptor Polymorphisms as Related toCancer Risk?Nicholas J. Rukin August 2007(II): S96 –S101Vol. 65, No. 8). In conclusion, the Fok polymorphism yields a 424 VDR variant somewhat more active than the 427 variant in terms of its transactivation capacity as a transcription factor. (Uitterlinden et al. / Gene 338 (2004) 143–156) The Taq and Bsm situation is even more complicated. Both are in a regulatory portion of the protein and the SNP changes do not affect the protein per se but they both affect a regulatory string of A’s in the sequence. Thus the presence or absence of the Bsm and Taq sites affects the number of A’s in the protein. Since Bsm and Taq have inverse effects both Bt and bT impact the number of A’s. The number of A’s in turn affects the stability of the information to make the VDR protein. As with everything else related to VDR, there is disagreement whether the shorter stretch of A’s (Bt) or the longer stretch of A’s (bT) grants more stability to the protein. Reports regarding which genotype is associated with a range of diseases or health conditions vary depending on the researcher. To try to keep things clear, in the future we will use the tt or TT designation to denote VDR Taq and FF and ff for Fok. Those who are tt should consider limited methyl donors. Those who are TT tend to have a greater tolerance for ie methylB12. Again, the bottom line is that I do feel low dose vitamin D plus rosemary and sage and resveratrol are a positive for all. This is especially true as there is conflicting literature regarding disease susceptibility and the various VDR SNPS that at times is totally contradictory.