title: Genetic polymorphisms of patients on stable warfarin maintenance therapy in a Ghanaian population.
abstract: BACKGROUND
  Warfarin is a widely prescribed anticoagulant with narrow therapeutic window for thromboembolic events. Warfarin displays large individual variability in dose requirements. The purpose of this study is to assess the contribution of patient-specific and genetic risk factors to dose requirements of patients on either high or low warfarin maintenance dose in Ghana. Blood samples were collected from 141 (62 males, 79 females) Ghanaian patients on stable warfarin dose to determine their INR. Influence of patient specific factors and gene variations within VKORC1, CYP2C9 and CYP4F2 were determined in patients on either high or low warfarin maintenance dose.
  
  
  RESULTS
  One hundred and forty-one patients took part in the study with 79 (56%) participants being Female. The median age of the study participants was 48 years [IQR: 34-58]. The median duration for patients to be on warfarin therapy was 24 months [IQR: 10-72]. Majority of the study participants (80.9%, n = 114) did not have any side effects to warfarin. CYP2C9*2 and CYP2C9*3 variant alleles were not detected. VKORC1 variant allele was observed at 6% and CYP4F2 variant allele was observed at 41%. Duration of patients on warfarin therapy was marginally associated with high warfarin dose (adjusted OR = 1.01 [95% CI 1.00-1.02], p = 0.033) while the odds of heterozygous individuals (G/A) for VKORC1 gene to have high warfarin dose compared to persons with homozygous (G/G) (adjusted OR = 0.06 [95% CI 0.01-0.63], p = 0.019). Age, gender, diagnosis, presence of side effects and other medications were not associated with warfarin dose (p = 0.05).
  
  
  CONCLUSIONS
  This study provides data on VKORC1 and CYP4F2 variants among an indigenous African population. Duration of patients on warfarin therapy was marginally associated with high warfarin dose. CYP2C9*2 and *3 variants were not detected and may not be the most important genetic factor for warfarin maintenance dose among Ghanaians.
authors.affiliation: Centre for Tropical Clinical Pharmacology and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, P.O. GP 4236, Accra, Ghana. wkudzi@yahoo.com.
authors.forename: William
authors.initials: W
authors.lastname: Kudzi
authors.affiliation: Centre for Tropical Clinical Pharmacology and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, P.O. GP 4236, Accra, Ghana.
authors.forename: Samuel Yao
authors.initials: SY
authors.lastname: Ahorhorlu
authors.affiliation: Department of Medical Biochemistry, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. GP 143, Accra, Ghana.
authors.forename: Bartholomew
authors.initials: B
authors.lastname: Dzudzor
authors.affiliation: Department of Haematology, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, P.O. GP 4236, Accra, Ghana.
authors.forename: Edeghonghon
authors.initials: E
authors.lastname: Olayemi
authors.affiliation: Centre for Tropical Clinical Pharmacology and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, P.O. GP 4236, Accra, Ghana.
authors.forename: Edmund Tetteh
authors.initials: ET
authors.lastname: Nartey
authors.affiliation: Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. GP 143, Accra, Ghana.
authors.forename: Richard Harry
authors.initials: RH
authors.lastname: Asmah
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000925:Anticoagulants / Q000627:therapeutic use*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D000072470:Cytochrome P450 Family 4 / Q000235:genetics; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005869:Ghana; D006579:Heterozygote; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012923:Social Class; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D014859:Warfarin / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: Allele frequencies; CYP2C9; CYP4F2; Pharmacogenetics; VKORC1; Warfarin