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Background  A  C1173T  polymorphism in intron 1 of the  VKORC1  gene has been claimed to determine the interindividual variability in the response to vitamin K antagonist therapy (VKA), but it is unknown whether it also influences bleeding risk. We aimed to confirm the relationship between  C1173T  status and phenprocoumon or acenocoumarol use, and to examine the risk of severe bleeding for the various genotypes.    Methods and Findings  We studied this in a case-control study of 110 patients who bled during VKA therapy and 220 control patients free of bleeding under the same therapy. To achieve the same target INR, CT genotype and TT genotype control patients required less phenprocoumon (CC genotype 2.9 mg/d [95% confidence interval (CI): 2.6–3.2], CT genotype 2.6 mg/d [95% CI: 2.1–3.1], TT genotype 1.4 mg/d [95 % CI: 1.1–1.7]) or acenocoumarol (CC genotype 3.2 mg/d [95% CI: 2.9–3.5], CT genotype 2.3 mg/d [95% CI: 2.1–2.5], TT genotype 1.7 mg/d [95% CI: 1.3–2.1]) than CC genotype control patients. Compared with CC genotype individuals, carriers of at least one T allele had an increased risk of bleeding in the phenprocoumon users (crude odds ratio = 2.6, 95% CI: 1.2–5.7), but not in acenocoumarol users (crude odds ratio = 1.2, 95% CI: 0.6–2.3).    Conclusion  These findings encourage taking further steps towards the evaluation of the use of  VKORC1  genetic testing for bleeding prevention in individuals who receive VKA therapy.

A C1173T Dimorphism in the VKORC1 Gene Determines Coumarin Sensitivity and Bleeding Risk