title: Evaluation of the effects of VKORC1 polymorphisms and haplotypes, CYP2C9 genotypes, and clinical factors on warfarin response in Sudanese patients.
abstract: OBJECTIVE
  African populations, including the Sudanese, are underrepresented in warfarin pharmacogenetic studies. We designed a study to determine the associations between the polymorphisms and haplotype structures of CYP2C9 and VKORC1 and warfarin dose response in Sudanese patients, one of the most genetically diverse populations in Africa.
  
  
  METHODS
  The effect of the CYP2C9 polymorphisms (*2, *3, *5, *6, *8, *9, and *11), 20 VKORC1 tag SNPs and haplotypes, and clinical covariates were comprehensively assessed in 203 Sudanese warfarin-treated patients.
  
  
  RESULTS
  Patients with the CYP2C9*2,*5,*6, or *11 variant required a daily warfarin dose that was 21% lower than those with CYP2C9*1/*1 (4.7 vs 5.8 mg/day, P < 0.001). SNPs around the VKORC1 and POL3S genes were divided into two haplotype blocks in Sudanese populations. According to multiple linear regression results, rs8050984, rs7294, and rs7199949 in the VKORC1 and POL3S genes (P <0.001, <0.001, <0.001, respectively), CYP2C9 genotype (*2, *5, *6, *11; P < 0.001), body weight (P = 0.04), target INR (P = 0.007), and concurrent medications (P = 0.029) could explain about 36.7% of the total warfarin dose variation.
  
  
  CONCLUSIONS
  Our data revealed that VKORC1 and CYP2C9 polymorphisms are important factors that influence warfarin dose response in Sudanese patients. Our data suggest that combinations of the SNPs may improve predictions of warfarin dose requirements.
authors: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, #50 Ilwon-dong, Gangnam-gu, Seoul 135-710, South Korea.
authors: Nassr Eldin M A
authors: NE
authors: Shrif
authors: Hong-Hee
authors: HH
authors: Won
authors: Seung-Tae
authors: ST
authors: Lee
authors: Jun-Hee
authors: JH
authors: Park
authors: Ka-Kyung
authors: KK
authors: Kim
authors: Min-Ji
authors: MJ
authors: Kim
authors: Seonwoo
authors: S
authors: Kim
authors: Soo-Youn
authors: SY
authors: Lee
authors: Chang-Seok
authors: CS
authors: Ki
authors: Ihsan M
authors: IM
authors: Osman
authors: Enaam A
authors: EA
authors: Rhman
authors: Ibtisam A
authors: IA
authors: Ali
authors: M N A
authors: MN
authors: Idris
authors: Jong-Won
authors: JW
authors: Kim
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