Limitations of VKORC1 rs9934438 as a Surrogate Marker for Vitamin K Antagonist Dose Adjustment.

VKORC1

The VKORC1 promoter variant rs9923231 determines sensitivity to vitamin K antagonists; the intronic variant rs9934438, assumed to be in strong linkage disequilibrium with it, is sometimes used as a surrogate.

The VKORC1 promoter variant rs9923231 is the reference marker for genotype-guided vitamin K antagonist dosing, yet the intronic variant rs9934438 is sometimes used as a surrogate. This retrospective single-centre study genotyped both variants in 939 patients using a TaqMan OpenArray custom panel. Concordance was high overall, but rs9934438 misclassified two patients who, according to rs9923231, required a reduced dose, i.e. potential false negatives. The authors support the preferential use of rs9923231.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The issue is mostly technical: two discordances among 939 patients do not call existing panels into question, but they are a reminder that a surrogate marker must be validated before replacing the causal variant in a test. The practical message is to target rs9923231 directly whenever possible.

Analysis by Dr Thibaut Benquey