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Background  In order to provide a cost-effective tool to analyse pharmacogenetic markers in malaria treatment, DNA microarray technology was compared with sequencing of polymerase chain reaction (PCR) fragments to detect single nucleotide polymorphisms (SNPs) in a larger number of samples.    Methods  The microarray was developed to affordably generate SNP data of genes encoding the human cytochrome P450 enzyme family ( CYP ) and  N -acetyltransferase-2 ( NAT2 ) involved in anti-malarial drug metabolisms and with known polymorphisms, i.e.  CYP2A6, CYP2B6 ,  CYP2C8 ,  CYP2C9 ,  CYP2C19 ,  CYP2D6 ,  CYP3A4 ,  CYP3A5 , and  NAT2 .    Results  For some SNPs, i.e.  CYP2A6*2 ,  CYP2B6*5 ,  CYP2C8* 3,  CYP2C9*3/*5 ,  CYP2C19*3 ,  CYP2D6*4  and  NAT2*6/*7/*14 , agreement between both techniques ranged from substantial to almost perfect (kappa index between 0.61 and 1.00), whilst for other SNPs a large variability from slight to substantial agreement (kappa index between 0.39 and 1.00) was found, e.g.  CYP2D6*17  (2850C>T),  CYP3A4*1B  and CYP3A5*3.    Conclusion  The major limit of the microarray technology for this purpose was lack of robustness and with a large number of missing data or with incorrect specificity.

malaria journal

A microarray-based system for the simultaneous analysis of single nucleotide polymorphisms in human genes involved in the metabolism of anti-malarial drugs