High Frequency of CYP3A4*1B among Opiate Dependent Patients in MalaysiaNasir Mohamad1,2*, Nurfadhlina M2, Nazila T2, Ahmad A2, Nor Hidayah Abu Bakar3, Hussein H4, Khafidz I5 and Ismail R2,6
- *Corresponding Author:
- Nasir Mohamad
Department of Emergency Medicine/Institute for
Research in Molecular Medicine (INFORMM), School of Medical Sciences
Health Campus, Universiti Sains Malaysia
16150 Kubang Kerian, Kelantan, Malaysia
Received July 14, 2012; Accepted July 24, 2012; Published July 27, 2012
Citation: Mohamad N, Nurfadhlina M, Nazila T, Ahmad A, Abu Bakar NH, et al. (2012) High Frequency of CYP3A4*1B among Opiate Dependent Patients in Malaysia. J Addict Res Ther 3:130. doi:10.4172/2155-6105.1000130
Copyright: © 2012 Mohamad N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The sharing of injection needles among drug user is a leading cause for the spread of HIV/AIDS. Malaysia introduced methadone as a management of heroin dependents to reduce HIV spread. Methadone has variable pharmacokinetics and CYP3A4 has been implicated in its metabolism. The objective of this study therefore was to determine if polymorphisms exist with CYP3A4 among opiate users in Malaysia. This study was approved by Ethics Committees at University of Malaya and Universiti Sains Malaysia. Control subjects comprised blood donors, students and residents of a village. Opiate-dependents were from methadone clinics and drop-in centers. They signed a written-informed consent to participate and gave blood for DNA CYP3A4 genotyping. DNA was extracted using QIAgen DNA mini kit. A nested two-step allele specific PCR method was developed to detect CYP3A4*1B, CYP3A4*3, CYP3A4*4, CYP3A4*5, CYP3A4*6, CYP3A4*7, CYP3A4*8, CYP3A4*9, CYP3A4*10, CYP3A4*11, CYP3A4*12, CYP3A4*13, CYP3A4*14, CYP3A4*15 and CYP3A4*16. Normal controls comprised Malays, Chinese and Indians but opiate-dependent subjects were majority Malay males. Control subjects all carried the wild-type gene. Mutant CYP3A4*1B allele was found in 2.17% of opiate-dependent subjects. Our results revealed that CYP3A4 was not polymorphic among Malaysian Malays, Chinese and Indians who were not opiate-dependent. To date, we are not aware of any study to associate CYP3A4 polymorphism and heroin addiction. It is conceivable that altered CYP3A4 function may contribute towards addiction liabilities in subsets of individuals. We conclude that CYP3A4 is polymorphic among heroin-dependent individuals. The mutation, CYP3A4*1B is not silent. This may have implications on heroin addiction liability as well as on dose requirements for MMT and HAART.