Research

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

Eva Maria Hodel^1* , Serej D Ley^1,4* , Weihong Qi^1,5 , Frédéric Ariey² , Blaise Genton^1,3 and Hans-Peter Beck¹

¹  Swiss Tropical Institute, Socinstrasse 57, PO Box, 4002 Basel, Switzerland

²  Institut Pasteur in Cambodia, Phnom Penh, Cambodia

³  Department of Ambulatory Care and Community Medicine, University of Lausanne, Lausanne, Switzerland

⁴  Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea

⁵  Functional Genomics Center Zurich, Zurich, Switzerland

author email corresponding author email* Contributed equally

Malaria Journal 2009, 8:285doi:10.1186/1475-2875-8-285

Published:	9 December 2009

Abstract

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.