Frequency of Cytochrome P450 2C9 (CYP2C9) Alleles in Three Ethnic Groups in Malaysia

Cytochrome P450 2C9 (CYP2C9) is the major enzyme involved in the metabolism of S-warfarin, an oral anticoagulant drug. Genetic polymorphisms of CYP2C9 gene have been reported and may play significant roles in pharmacogenomics. To date, over 5 CYP2C9 allelic variants have been reported. The most common allelic variants identified include CYP2C9*2 and CYP2C9*3. We conducted an investigation to determine the CYP2C9 genetic polymorphisms in a portion of the Malaysian population comprising of three major ethnic groups and compared the frequencies with other populations. Molecular typing of CYP2C9*1, CYP2C9*2 and CYP2C9*3 was carried out in 337 subjects (inclusive of patients on warfarin treatment and healthy normal control) by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism). This represents the first investigation of CYP2C9 genetic polymorphisms in Malaysia. Two hundred and ninety eight subjects were identified as homozygous CYP2C9*1 from this study. Eleven percent of subjects were heterozygous for CYP2C9*2 or/and CYP2C9*3 allelic variants. Six subjects were CYP2C9*1/*2 heterozygotes, 29 subjects were CYP2C9*1/*3 heterozygotes, 2 subjects were CYP2C9*2/*3 heterozygotes. Of the 337 study subjects, only 2 were CYP2C9*3 homozygotes. In this study, we found that there was no homozygous CYP2C9*2 subjects. The CYP2C9*1 allele frequencies of Malays, Chinese and Indians were 0.9407, 0.9764 and 0.875 respectively. CYP2C9*2 was not detected in the Malays and Chinese, but was present in the Indians with a frequency of 0.0435. The frequency of CYP2C9*3 was the highest in Indians (0.0815) followed by Malays (0.0593) and Chinese (0.0236). Our results suggest that CYP2C9*1 is the predominant allele in all the three ethnic groups. Although CYP2C9*2 is very common in Caucasians, it is rarely found in Chinese and Malay ethnic groups. The frequencies of CYP2C9*3 in Caucasians have been reported to be higher compared to Asian populations; but the frequencies of Malays and Indians in our study were in the range of Caucasians (6-10%).