[olsen]

For individuals who have access to their SNPs:

Another SNP related to B12:

TCN2 gene - transcobalamin II

rs1801198 Result: CG (heterozygous). ~42% of EU.
aka: C776G, P259R.
CG and GG results carry increasing risk here.

CC (wildtype) is 22-33% of EU.
CG is 42% of EU.
GG is 16-25% of EU.

Newman, Gordon, Suen (2004), citing Miller et al, note that
methylmalonate in organic acids testing is a reliable index of
defective enzyme activity, namely transcobalamin II (TCII), responsible
for transporting B12 from the ileum (end of small intestine where
it joins the colon, near the appendix) to the tissues. Variation in
enzyme activity in TCII is due to the 776C>G polymorphism (rs1801198),
which results in decreased binding affinity of the enzyme for B12
with consequent compromised delivery of B12 to tissues, and overall
decrease in B12 functional status. Mutations in the rs1801198 SNP
will be reflected in higher methylmalonic acid levels on organic acids
testing, possibly without variation/mutation in folate levels or genetics.
http://www.highbeam.com/doc/1G1-122581684.html


In vitamin-dependent or vitamin-responsive disorders, many of which are inheritable conditions, use of pharmacological doses of a vitamin, sufficiently overcome the metabolic blockage for normal function to occur with symptom resolution, in many instances. Multiple carboxylase deficiency, megaloblastic anemia, methylmalonic aciduria, and B6-responsive anemia are just a few well-known disorders that respond favorably to pharmacological doses of vitamins. And, new is the identification of single nucleotide polymorphisms (SNP's). With the advent of genomics and identification of SNP's related to variant enzyme activity, it is estimated that as many as one-third of single mutations in a gene result in the corresponding enzyme having a decreased binding affinity for its coenzyme, resulting in a lower rate of reaction. Administration of relatively high doses of the vitamin component of the corresponding coenzyme serves to restore enzymatic activity for many inheritable defects due to SNP's. (2)

Methylmalonic acid (methylmalonate), for example, has long been known as a marker for vitamin B12 deficiency. As serum levels of cobalamin (B12) decrease, levels of urinary methylmalonate increase. Therefore, methylmalonate serves as an effective marker for B12 deficiency. The research of Miller et al., have recently shown that methylmalonate is a reliable index of defective enzyme activity, namely transcobalamin II (TCII), responsible for transporting B12 from the ileum to the tissues. Apparently, variant enzyme activity in TCII is due to a single nucleotide polymorphism (SNP) at base position 776 in the DNA sequence in which a G-to-C substitution results in the synthesis of this enzyme carrying an arginine residue in place of proline at codon position 259. This common polymorphism results in a decreased binding affinity of the enzyme for B12 with consequent compromised delivery of B12 to tissues, and overall decrease in B12 functional status. (3) Other SNP-organic acid relationships have not been elucidated to this degree, but it does add to the potential value in organic acid testing.

http://66.197.58.78/inborn_error_of_..._article_1.htm