Warfarin has been the most trusted but challenging
anticoagulant in clinical practice for the last seven decades. The challenge is
to manage its dose. A narrow therapeutic index and high inter- and
intra-individual variability in drug disposition and response are the factors
that shift the pendulum to adverse drug events from one end of fatal hemorrhage
to the other i.e. thrombosis. The difficult task for clinical management is to
maintain the required international normalized ratio (INR) with warfarin therapy.
Factors responsible for this difficult task include both genetic and
non-genetic. The predominant genes are those coding for vitamin K epoxide
reductase complex (VKORC) subunit 1 (VKORC1; the target of warfarin and the
enzyme of warfarin metabolism; cytochrome P450 enzyme 2C9 (CYP2C9). There is
general agreement among published retrospective population studies that the
combination of VKORC1 and CYP2C9 genotypes, together with gender, age, body
mass index or height or weight and concurrent medications, predict
approximately 50% of warfarin dose requirement. Thus, genetic testing will be
able to predict and help in directing toward the correct dose and reduce the
counts of trial and error as well as risks during therapy. Within the Asian
population, Indian patients have been reported to require higher warfarin doses
than others. Here we also review the prevalence of the genetic variations of
VKORC1 and CYP2C9 associated with variable warfarin response in Indian
populations from different regions and also depict studies that have aimed at
analysing the influence of genotypic variations to the clinical dose of
Warfarin in the Indian population.
Author(s) Details
Kavita Shalia
Sir H. N. Medical Research Society, Sir H. N. Hospital and Research Centre,
Court House, L. T. Road, Mumbai 400002, India.
Sunila Raju
Sir H. N. Medical Research Society, Sir H. N. Hospital and Research Centre,
Court House, L. T. Road, Mumbai 400002, India.
Amit Chandan
Sir H. N. Reliance Foundation Hospital and Research Centre, Raja Rammohan
Roy Road, Mumbai 400004, India.
Please see the link:- https://doi.org/10.9734/bpi/mmrnp/v1/1194
