Pharmacogenetic typing for oral anti-coagulant response among factor V Leiden mutation carriers

Factor V Leiden mutation is the most common inherited predisposition for hypercoagulability and thereby a common genetic cause for initiation of oral anti-coagulation therapy. There is a dearth of knowledge of coumarin response profile in such thrombophilic population.

The current pilot study aims to estimate coumarin sensitivity in an Indian cohort with an inherited thrombophilia risk factor (Factor V Leiden mutation carriers) based on the observed frequency of CYP2C9 (*)2, (*)3 and VKORC1-1639G >A genotype combinations.

A retrospective study carried out in a tertiary health care center in India.

Carriers of FVL mutation were genotyped for CYP2C9 ((*)2, F(*)3) and VKORC1 (-1639G >A) variants by PCR-RFLP technique.

Chi-square test to analyze difference in expected and observed genotype frequency.

Sixty-one (n = 61) unrelated carriers of FVL mutation were observed in the 13 years study period. The allele frequency of CYP2C9 (*)2, CYP2C9 (*)3, and VKORC1-1639A in this cohort was 0.06, 0.11, and 0.16, respectively. Six (9.7%) individuals had two of the three variant alleles (heterozygous or homozygous), and 28 (45.9%) were heterozygous for at least one polymorphism.

Pre-prescription genotyping for coumarin drugs, if introduced in Indians with inherited thrombophilia (in whom oral anti-coagulant therapy may be necessary), is likely to identify 9.7% (hypersensitive) subjects in whom the optimum anti-coagulation may be achieved with reduced dosages, 44.3% (normal sensitivity) who may require higher dose and also 55.6% (hyper and moderate sensitivity) subjects who are likely to experience bleeding episodes.