Zainuddin Z, Teh L K, Suhaimi A W M, Ismail R
Pharmacogenetics Research Group, Institute for Research in Molecular Medicine, INFORMM, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
J Clin Pharm Ther. 2006 Apr;31(2):187-91. doi: 10.1111/j.1365-2710.2006.00727.x.
CYP2C9 is one of the major drug metabolizing enzymes for many drugs including warfarin, NSAIDs and losartan. It is polymorphic in many populations. Data on the distribution of CYP2C9 and the implication of CYP2C9 polymorphism in the Malaysian population is lacking. Our objectives were therefore to investigate the prevalence of CYP2C9 variants among unrelated healthy volunteers of Malays, Chinese and Indians in Malaysia.
Deoxyribonucleic acid was extracted using standard lysis methods. Allele specific polymerase chain reaction was performed for determination of CYP2C9*1, *2, *3, *4 and *5 variants according to Z. Zainuddin, L.K. Teh, A.W.M. Suhaimi, M.Z. Salleh, R. Ismail (2003, Clinica Chimica Acta, 336, 97).
The Chinese had the highest frequency of CYP2C91 (321/330, 97.27%), followed by the Malays and the Indians (402 of 420, 95.71% and 291 of 330, 88.18%, respectively). CYP2C92 was not found in the Chinese. CYP2C93 were detected in all the three races with the Indians having the highest frequency of CYP2C93 (9.7%). The Indians had a frequency of CYP2C9*2 and *3 similar to Tamilians and Caucasians. Two of the Indians had *2/*3 and one had *3/3 genotypes and are likely to be slow metabolizers. No subject with CYP2C94 and *5 were detected in our populations.
CYP2C9*2 and *3 were identified in our population. Indians are similar to Caucasians in terms of CYP2C9 genotypes and thus may respond to CYP2C9 substrates differently when compared with the Malays and Chinese in Malaysia.
细胞色素P450 2C9(CYP2C9)是包括华法林、非甾体抗炎药和氯沙坦在内的多种药物的主要药物代谢酶之一。它在许多人群中具有多态性。马来西亚人群中关于CYP2C9分布以及CYP2C9多态性影响的数据尚缺乏。因此,我们的目标是调查马来西亚马来人、华人及印度人非亲属健康志愿者中CYP2C9变异体的患病率。
采用标准裂解方法提取脱氧核糖核酸。根据Z. Zainuddin、L.K. Teh、A.W.M. Suhaimi、M.Z. Salleh、R. Ismail(2003年,《临床化学学报》,336卷,97页)的方法,进行等位基因特异性聚合酶链反应以测定CYP2C9*1、*2、*3、4和5变异体。
华人中CYP2C91的频率最高(321/330,97.27%),其次是马来人和印度人(分别为420人中的402人,95.71%;330人中的291人,88.18%)。华人中未发现CYP2C92。在所有三个种族中均检测到CYP2C93,其中印度人CYP2C93的频率最高(9.7%)。印度人CYP2C92和3的频率与泰米尔人和高加索人相似。两名印度人具有2/3基因型,一名具有3/3基因型,可能是慢代谢者。在我们的人群中未检测到携带CYP2C94和5的受试者。
在我们的人群中鉴定出了CYP2C92和3。在CYP2C9基因型方面,印度人与高加索人相似,因此与马来西亚的马来人和华人相比,他们对CYP2C9底物的反应可能不同。