Journal of postgraduate medicine · 2012
Haplotypes frequencies of CYP2B6 in Malaysia.
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Musa N, Zulkafli M I, Talib N, Mohamad N, Fauzi H, Ismail R
Аннотация
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.
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.