Frequency of Common CYP2C9 Polymorphisms and Their Impact on Warfarin Dose Requirement in Pakistani Population.
Polymorphisms in cytochrome P450 (CYP) 2C9 (CYP2C9) gene result in interindividual variability in warfarin dose requirement. There is a need for characterization of genotype frequency distribution in different populations for construction of customized dosing algorithms to enhance the efficacy and reduce the toxicity of warfarin therapy. This study was carried out in Pakistani population to evaluate the contribution of common CYP2C9 polymorphisms to warfarin therapy. A total of 550 stable patients taking warfarin were enrolled after medical history, physical examination, and laboratory investigations. Single blood sample was collected after informed consent. Genomic DNA was extracted, and genotype analysis for CYP2C9*2 and CYP2C9*3 polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism assay. A number of samples were also analyzed by direct DNA sequencing for validation of the results. Data were analyzed using SPSS version 20. Genotype frequency distribution of CYP2C9*2 and CYP2C9*3 was found to be different from other populations. Of these 2 polymorphisms, CYP2C9*2 did not demonstrate significant effect on warfarin dose requirement, whereas CYP2C9*3 did show significant effect ( P value = .012). It is concluded that there is a need to study genotype frequency distribution and their effect on warfarin dose variability among different populations due to diversity in outcome.
1 Department of Pharmacology, Fazaia Medical College, Air University, Islamabad, Pakistan.
Aisha
A
Qayyum
2 Department of Pharmacology, Foundation University Medical College, Islamabad, Pakistan.
Muzammil Hasan
MH
Najmi
3 Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan.
Qaisar
Q
Mansoor
4 Department of Medical Technology, ShifaTameer-e-Millat University, Islamabad, Pakistan.
Zia-Ur-Rehman
ZU
Farooqi
5 Department of Biochemistry, Islamic International Medical College, Riphah International University, Rawalpindi, Pakistan.
Abdul Khaliq
AK
Naveed
3 Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan.
Andleeb
A
Hanif
3 Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan.
Syed Ali Raza
SAR
Kazmi
3 Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan.
Muhammad
M
Ismail
D000293:Adolescent; D000328:Adult; D000368:Aged; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D054796:Drug Dosage Calculations; D005787:Gene Frequency; D006801:Humans; D008875:Middle Aged; D010154:Pakistan / Q000453:epidemiology; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D014859:Warfarin / Q000008:administration & dosage*; D055815:Young Adult
D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9
CYP2C9 polymorphism; CYP2C9*2; CYP2C9*3; PCR-RFLP; direct DNA sequencing; warfarin