Abstract:
Variations of cytochrome-P450 enzyme system (CYP2CP) are associated with impaired metabolism of
warfarin. The objective of our study was to estimate the frequency of genetic and allelic variants of CYP2C9 in
Punjabi population of Pakistan and their effects on warfarin dose requirement. One hundred and twenty
unrelated Pakistani subjects belong to Punjab province, were randomly included from the registry of National
Institute of Heart Disease Rawalpindi, Pakistan. The patients had stable international normalized ratio (INR) of
2 to 3 for last 3 months with warfarin therapy after heart valves replacement. The detection of CYP2C9 variant
was done on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Total
120 patients (73 males; 47 females) of mean age of 37 years participated in the study. Nine patients had mutant
allele CYP2C9*3 (7.5%), one CYP2C9*2 (0.8%) and 110 patients exhibited wild type CYP2C9*1 (91.7%).
The frequency of CYP2C9 genotype was *1/*1 (0.858) ; *1/*3 (0.117) ; 2/*20 (0.08 ) and *3/*3 (0.017) in our
study population. A high dose of warfarin (42.2+9.56) mg/week is required for patients with *1/*1 genotype as
compared to patients with *2/*2 (17.5+1.9) and *1/*3 (16.6+2.3) allele (p<0.001). Individuals with
CYP2C9*3/3* need lowest (8.75±1.76 mg/week) daily warfarin dose. In conclusion, the genetic variations in
the CYP2C9 occur in 14% of Punjabi ethnic group in Pakistan. Presence of CYP2C9*2 or *3 variants is an
independent predictor of low warfarin dose requirement in our patients. CYP2C9 variants assay may be used in high risk groups for appropriate dose adjustment to avoid complications on long term basis.
