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© Copyright 2004 The British Pharmacological Society

169P University of Newcastle
Winter Meeting December 2004

Frequency of CYP2C9 genotypes among Omani patients receiving warfarin

Musbah O. Tanira1, Mohammed K. Al-Mukhaini2, Ali T. Al-Hinai1, Khalid A. Al Balushi1& Ikhlas S. Ahmed1. 1College of Medicine & Health Sciences, Sultan Qaboos University and 2Royal Hospital, Ministry of Health, Sultanate of Oman.

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Tanira MO
Al-Mukhaini MK
Al-Hinai AT
Al Balushi KA
Ahmed IS

Cytochrome P450 2C9 isoenzyme (CYP2C9) metabolizes S-warfarin. CYP2C9 gene polymorphism may lead to variable patient response to the drug. CYP2C9*2 and CYP2C9*3 alleles are associated with decreased enzymatic activity. In this study, we determined the frequencies of CYP2C9 allele variants in Omani patients (189 patients) receiving warfarin on a long-term basis. Data from patients with INR values between 2.0 and 4.0 who had no co-morbid conditions (142 patients) were used in genotyping/dosage data analysis. CYP2C9 genotypes were determined by a PCR-RFLP method as described elsewhere [1, 2]. DNA was isolated from whole blood samples from these patients using a Qiagen® DNA extraction kit.

Genotyping data showed that 12.7 % and 5.8 % of the samples were heterozygous for the CYP29*2 and CYP2C9*3 alleles, respectively. Two subjects were homozygous for the CYP2C9*2 allele and no CYP2C9*3 homozygous subjects were detected. The CYP2C9*2 allele frequency was 0.074 in our population, whereas it was 0.029 for CYP2C9*3. The latter frequency was similar to that of Asian populations (0.020–0.050) and lower than that of Caucasian populations (0.060–0.100). The total frequency of CYP2C9 variant genotypes appeared to be 20.0%, implying that these patients may be slow metabolizers of warfarin, and thus may be at a higher risk of bleeding. This is the first report on the presence of CYP2C9*2 allele homozygocity in any Asian or African population, and is the first to report on the presence of this variant in an Asian population.

Table 1
Genotype frequencies among 189 Omani patients receiving warfarin*

Genotype Frequency
CYP2C9*1/*1 80.4%
CYP2C9*1/*2 12.7%
CYP2C9*1/*3 5.8%
CYP2C9*2/*2 1.1%

* No CYP2C *2/*3 and CYP2C9*3/*3 were detected

1. Goldstein JA. Br J Clin Pharmacol 2002; 53: 409.
2. Stubbins MJ, et al. Pharmacogenetics 1996; 6: 429.