MedWire News: Warfarin metabolism in Japanese people is not influenced by mutations in the vitamin K epoxide reductase complex subunit 1-like 1 (VKORC1L1) gene, research shows.

VKORC1L1 is a paralogous gene of VKORC1, sharing 50% of its amino acid sequence, Toshiyuki Miyata (National Cardiovascular Center, Osaka, Japan) and colleagues explain.

Recognizing that single nucleotide polymorphisms (SNPs) in VKORC1 are responsible for a significant proportion of the variation in warfarin maintenance dose requirements, the team examined whether VKORC1L1 plays a similar role.

The researchers recruited 87 patients and used a stable anticoagulant dose to maintain an international normalized ratio of 1.6-2.6. They examined the patients for eight SNPs in the VKORC1L1 gene in three haplotype blocks.

However, none of the haplotypes or SNPs were significantly related to the patients' daily maintenance dose requirements, the team reports in the journal Thrombosis Research.

Hypothesizing that a functional SNP in VKORC1 (1173C-to-T) and on the cytochrome P450 2C9 gene (CYP3C9*3) could mask any effect of VKORC1L1 on warfarin dose requirement, the team examined maintenance dose variability in patients without these additional SNPs. Again no link between dose and VKORC1L1 variation was found.

Miyata et al therefore conclude:"VKORC1L1 is not likely to be involved in the inter-individual variability of the therapeutic dose of warfarin."

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