The Prevalence of CYP2B6 Gene Polymorphisms in Malaria-endemic Population of Timor in East Nusa Tenggara Indonesia

Objectives The CYP2B6 is one of the most polymorphic CYP genes in humans that has the potential to modify the pharmacological and toxicological responses to clinically important drugs such as antimalarial artemisinin and its derivatives. The aim of the study was to determine the frequency of CYP2B6 polymorphisms in Timor malaria endemic area, East Nusa Tenggara, Indonesia where Artemisin-based Combination Therapy (ACT) has been used to treat uncomplicated malaria. Methods A total of 109 healthy subjects were participated in this study. CYP2B6*4, *6 and *9 polymorphisms were analyzed using PCR-RFLP to confirm the SNPs prevalence of 516G>T and 785A>G in exon 4 and 5. Results There were 96 subjects included in the analysis. In the exon 4 of CYP2B6 516G>T, the frequency of the T mutation was 37.5% (39/96), and the wildtype 27.1% (26/96). In the exon 5, CYP2B6 785A>G mutant was detected in 29.2% (28/96) of individuals, and the wildtype allele in 35.4% (34/96). The frequency of CYP2B6*9 (516G>T), CYP2B6*4 (785A>G) and CYP2B6*6 (516G>T and 785A>G) were 40.6%, 29.2% and 22.9%, respectively. The prevalence of these CYP2B6 gene polymorphisms in Timorian ethnic were higher than that in Malay, Han Chinese, Indian, and Egyptian populations. Conclusion The prevalence of these CYP2B6 516G>T and 785A>G polymorphisms in Timorian ethnic is higher than that in other populations. These polymorphisms may affect the metabolism of artemisinin and its derivatives.

[1]  S. Zakeri,et al.  Genetic variability of CYP2B6 polymorphisms in southeast Iranian population: implications for malaria and HIV/AIDS treatment. , 2014, Archives of Iranian medicine.

[2]  P. Suffys,et al.  Frequencies of Cytochrome P450 2B6 and 2C8 Allelic Variants in the Mozambican Population. , 2013, The Malaysian journal of medical sciences : MJMS.

[3]  Ulrich M. Zanger,et al.  Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance , 2013, Front. Genet..

[4]  Shakir Ali,et al.  Prevalence of poor and rapid metabolizers of drugs metabolized by CYP2B6 in North Indian population residing in Indian national capital territory , 2012, SpringerPlus.

[5]  R. Ismail,et al.  Haplotypes frequencies of CYP2B6 in Malaysia. , 2012, Journal of postgraduate medicine.

[6]  J. Olson,et al.  Allele and Genotype Frequencies of CYP2B6 and CYP2C19 Polymorphisms in Egyptian Agricultural Workers , 2012, Journal of toxicology and environmental health. Part A.

[7]  D. Ballou,et al.  Polymorphic Variants of Cytochrome P450 2B6 (CYP2B6.4–CYP2B6.9) Exhibit Altered Rates of Metabolism for Bupropion and Efavirenz: A Charge-Reversal Mutation in the K139E Variant (CYP2B6.8) Impairs Formation of a Functional Cytochrome P450-Reductase Complex , 2011, Journal of Pharmacology and Experimental Therapeutics.

[8]  X. Su,et al.  Discovery, mechanisms of action and combination therapy of artemisinin , 2009, Expert review of anti-infective therapy.

[9]  S. Oka,et al.  Allele and Genotype Frequencies of Cytochrome P450 2B6 Gene in a Mongolian Population , 2009, Drug Metabolism and Disposition.

[10]  J. Halpert,et al.  Decreased Susceptibility of the Cytochrome P450 2B6 Variant K262R to Inhibition by Several Clinically Important Drugs , 2009, Drug Metabolism and Disposition.

[11]  Magnus Ingelman-Sundberg,et al.  Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. , 2007, Pharmacology & therapeutics.

[12]  Lang Li,et al.  Impact of CYP2B6 polymorphism on hepatic efavirenz metabolism in vitro. , 2007, Pharmacogenomics.

[13]  Xin Li,et al.  Intra- and Inter-ethnic Differences in the Allele Frequencies of Cytochrome P450 2B6 Gene in Chinese , 2006, Pharmaceutical Research.

[14]  M. Ziats,et al.  Prevalence of CYP2B6 alleles in malaria-endemic populations of West Africa and Papua New Guinea , 2006, European Journal of Clinical Pharmacology.

[15]  M. Eichelbaum,et al.  Multiple Novel Nonsynonymous CYP2B6 Gene Polymorphisms in Caucasians: Demonstration of Phenotypic Null Alleles , 2004, Journal of Pharmacology and Experimental Therapeutics.

[16]  Terry Crowley,et al.  The Oceanic Languages , 2001 .

[17]  U. Yasar,et al.  Role of polymorphic human CYP2B6 in cyclophosphamide bioactivation , 2003, The Pharmacogenomics Journal.