High prevalence of CYP2A6*4 and CYP2A6*9 alleles detected among a Malaysian population.
BACKGROUND
CYP2A6 gene encodes the principal enzyme involved in the metabolism of many drugs including artesunate. We developed a simplified duplex nested PCR method for the detection of the CYP2A61B, CYP2A62, CYP2A64, CYP2A67, CYP2A68 and CYP2A69 variant alleles highly prevalent among Malaysian population.


METHODS
Genomic DNA was isolated from peripheral blood of patients treated with artesunate by using a DNA extraction kit. Fragments from TATA box in 5' flanking region, exons 1 to 4 and exon 8 to 3' UTR of the gene were amplified using a first PCR step (PCR1). Products from PCR1 were then used to run a duplex PCR (PCR2) for detecting the selected variant alleles.


RESULTS
All 6 CYP2A6 alleles were successfully amplified and confirmed by sequencing. The frequency of the alleles were 14.6% for CYP2A61B, 16.7% for CYP2A64, 4.2% for CYP2A68 and 10.4% for CYP2A69.


CONCLUSIONS
High frequencies of the CYP2A64 and CYP2A69 alleles which contribute to the poor metabolism status may impact treatment of patients receiving drugs metabolized by CYP2A6 such as artesunate among Malaysians.
Yusof
Wardah
W
Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia. wadiecomel@yahoo.com
Gan
Siew Hua
SH
D000483:Alleles; D000655:Amodiaquine / Q000008:administration & dosage / Q000627:therapeutic use; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use; D000077332:Artesunate; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D065637:Cytochrome P-450 CYP2A6; D064420:Drug-Related Side Effects and Adverse Reactions; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008296:Malaysia; D016133:Polymerase Chain Reaction; D016032:Randomized Controlled Trials as Topic
D000962:Antimalarials; D037621:Artemisinins; D000655:Amodiaquine; D000077332:Artesunate; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6