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


CONCLUSIONS
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.
Hodel
Eva Maria
EM
Swiss Tropical Institute, Socinstrasse 57, PO Box, 4002 Basel, Switzerland.
Ley
Serej D
SD
Qi
Weihong
W
Ariey
Frédéric
F
Genton
Blaise
B
Beck
Hans-Peter
HP
D000962:Antimalarials / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D001191:Arylamine N-Acetyltransferase; D002160:Cambodia; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008288:Malaria / Q000188:drug therapy / Q000235:genetics / Q000469:parasitology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010961:Plasmodium / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000187:drug effects* / Q000235:genetics; D012680:Sensitivity and Specificity; D013636:Tanzania
D000962:Antimalarials; D003577:Cytochrome P-450 Enzyme System; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human