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Indian J Hum Genet. 2012 Sep;18(3):326-31. doi: 10.4103/0971-6866.107987.

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

Author information

  • 1Centre of Medical Genetics, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi ; Amity Institute of Biotechnology, Amity University, Uttar Pradesh, India.

Abstract

CONTEXT:

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.

AIMS:

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.

SETTINGS AND DESIGN:

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

MATERIALS AND METHODS:

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

STATISTICAL ANALYSIS USED:

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

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Acenocoumarol; India; bleeding; factor V Leiden; oral anti-coagulant; pharmacogenetic; prothrombin; thrombophilia; thrombosis; warfarin

PMID:
23716941
[PubMed]
PMCID:
PMC3656522
Free PMC Article
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