Haplotypes frequencies of CYP2B6 in Malaysia

J Postgrad Med. 2012 Oct-Dec;58(4):235-41. doi: 10.4103/0022-3859.105439.

Abstract

Background: Drugs with complex pharmacology are used in the management of drug use disorder (DUD) and HIV/AIDS in Malaysia and in parts of South-East Asia. Their multiethnic populations suggest complexity due to the genetic polymorphism, such as CYP2B6 that metabolizes methadone and anti-retroviral.

Aims: Our aim was to explore the genetic polymorphism of CYP2B6 among Malays, Chinese, Indians, and opiate-dependent individuals in Malaysia.

Settings and design: The study utilized DNA from our previous studies on CYPs and new recruitments from opiate-dependent individuals.

Materials and methods: For the new recruitment, after obtaining consent and baseline demography, 5 ml blood was obtained from patients attending methadone maintenance therapy (MMT) Clinics. Genomic DNA was extracted using standard methods. 10 nucleotide changes associated with CYP2B6*10, CYP2B6*2, CYP2B6*17, CYP2B6*11, CYP2B6*8, CYP2B6*14, CYP2B6*9, CYP2B6*4, CYP2B6*6, CYP2B6*27, and CYP2B6*20 were determined using multiplex nested allele-specific PCR.

Statistical analysis: Descriptive statistics were used to summarize demographic data. Differences in allele frequencies between populations were tested using Chi-squared test and were corrected using the Bonferroni test.

Results: CYP2B6 polymorphism in Malaysia is variable with trends that suggest an ethnic difference. Reduced activity CYP2B6*6 occurred in 13% to 26% among Malays, Chinese, Indians and opiate-dependent individuals. Another 'reduced activity', CYP2B6*2 allele, was found at much lower percentages in the groups.

Conclusions: The relative commonness of reduced-activity CYP2B6 alleles in our study called for attention in terms of dosage requirements for MMT and ARV in Malaysia. It also implored follow-up association studies to determine its relevance and consequences in personalized medicine for drug use disorder and HIV/AIDS.

MeSH terms

  • Adult
  • Algorithms
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Asian People / genetics*
  • China
  • Cytochrome P-450 CYP2B6
  • Female
  • Gene Frequency*
  • Haplotypes*
  • Heroin Dependence / drug therapy*
  • Humans
  • India
  • Malaysia / ethnology
  • Male
  • Methadone / therapeutic use*
  • Opiate Substitution Treatment
  • Oxidoreductases, N-Demethylating / genetics*
  • Oxidoreductases, N-Demethylating / metabolism
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*

Substances

  • Aryl Hydrocarbon Hydroxylases
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6
  • Oxidoreductases, N-Demethylating
  • Methadone