CYP2C9 polymorphism: prevalence in healthy and warfarin-treated Malay and Chinese in Malaysia.
BACKGROUND
Genetic polymorphisms of CYP2C9 among different populations in different geographical regions could be different. CYP2C9 has been reported to be the enzyme responsible for the metabolism of many drugs, including warfarin and other drugs with a narrow therapeutic index. Realising the importance of inter-individual differences in the genetic profile in determining the outcome of a drug therapy, this study was conducted to explore the types and frequencies of CYP2C9 alleles in healthy and warfarin-treated Malays and Chinese, the two major ethnic groups in Malaysia. We aimed to evaluate the prevalence of the types and frequencies of common CYP2C9 alleles (*1, *2, *3 and *4) among the healthy unrelated individuals and diseased patients prescribed with warfarin.


METHODS
A total of 565 Malay and Chinese subjects, including 191 patients prescribed warfarin, were recruited into the study. The healthy unrelated volunteers were also blood donors and they were confirmed to be physically fit before participating in the study. For the patients group, their medical records were reviewed for the relevant clinical data. 5 ml of blood was taken from each subject, and DNA was isolated and used for identification of the CYP2C9 allele *1, *2, *3 and *4 using nested-allele-specific-multiplex-polymerase chain reaction.


RESULTS
CYP2C9*1,*2 and *3 were detected among the healthy unrelated individuals but only CYP2C9*1 and *3 were found in the diseased patients. Among the healthy Malays, 92.8 percent had CYP2C9*1/*1, 2.6 percent had CYP2C9*1/*2 and 4.6 percent had CYP2C9*1/*3 genotypes. Among the Chinese, 92.3 percent had CYP2C9*1/*1 and 7.7 percent had CYP2C9*1/*3, but CYP2C9*2 and *4 were not found in the Chinese. Among the warfarin-treated group, only CYP2C9*1 and *3 were detected. Even though some alleles were not detected among the patients, suggesting the possible role of CYP2C9 in certain disorders, the sample size of the current study is too small to be able to arrive at any conclusive results.


CONCLUSIONS
Based on the above-observed genotypes, the prevalence of CYP2C9*2 and *3 was low in healthy and warfarin-treated Malays and Chinese in Malaysia. Further studies are required to support the clinical effectiveness of pharmacogenomics testing.
Ngow
H A
HA
Department of Internal Medicine, Faculty of Medicine, International Islamic University Malaysia/Hospital Tengku Ampuan Afzan, Jalan Istana, Bandar Indera Mahkota, Kuantan 25200, Malaysia. harrisngow@gmail.com
Wan Khairina
W M
WM
Teh
L K
LK
Lee
W L
WL
Harun
R
R
Ismail
R
R
Salleh
M Z
MZ
D000483:Alleles; D000925:Anticoagulants / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D065729:Cytochrome P-450 CYP2C9; D016903:Drug Monitoring; D006801:Humans; D008296:Malaysia / Q000208:ethnology; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D015995:Prevalence; D014859:Warfarin / Q000378:metabolism*
D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases