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Evolutionary Genomics and Bioinformatics Laboratory, Division of Genomics and Bioinformatics, National Institute of
Malaria Research, Sector-8, Dwarka, New Delhi-110077, India.
2
CMJ University, Shillong, Meghalaya, 793 003, India.
Considering malaria is a highly devastating disease of mankind, total eradication of malaria
seems to be an uphill task, the only relief from this disease is achieved by usage of antimalarial
drugs. Since malaria is associated with humans from time immemorial, usage of traditional
substances to most presently effective antimalarial have been recorded to cure this disease.
With the advent of modern biological techniques aided the understanding of the biochemical
pathways of antimalarial metabolism thereby helping in designing successful usage of many
antimalarials. Nevertheless, improper usages of certain drugs have led to the origin and spread
of drug resistant malaria parasites (chloroquine resistant Plasmodium falciparum). Also, the
genetic basis of antimalarial metabolism in humans is now well understood and frequent
mutations in genes of malarial parasites are well associated with drug resistance. The entire
scenario of antimalarial usage in the field have become complicated, partly due to poor
understanding between antimalarial metabolism in humans and drug fighting mechanism in
parasites, by which resistance to even combined therapy (e.g. Artemisinin Combination
Therapy) have started emerging. Vital basic understanding from human and parasite population
genetics (involving antimalarial both metabolizing genes in human and resistant genes in
parasite) could be an ideal starting point to malaria control.
Key words: Malaria, antimalarial drugs, metabolization, population genetics, pharmacogenomics
INTRODUCTION
Malaria is considered as one of the three most deadly
infectious diseases including Tuberculosis (T.B.) and
Human Immunodeficiency Virus (HIV) (Riley and Stewart,
2013) which has resulted in high mortality worldwide with
an estimated 3.3 million people at high risk malaria
(World Health Organization, 2013). It affects, mainly,
population residing in tropical and subtropical areas due
to the presence of suitable temperature and rainfall which
is required for the development of Plasmodium parasites
in female Anopheles mosquitoes (Gallup and Sachs,
2001). Over 90% of malaria sufferers are borne by
populations in Africa (Winstanley et al., 2004) and are
mainly children (<5 years) and pregnant women. Outside
002
003
Figure 1. Antimalarials metabolized by drug metabolizing gene (a. Primaquine, b. Artemisinin, c. Proguanil, d. Dapsone, e. Amodiaquine, f.
Chloroquine, g. Clindamycin, h. Mefloquine, i. Halofantrine and j. Sulphadoxine).
004
005
Figure 2. Gene location, Exon, Intron of drug metabolizing gene CYP1A2 located on human chromosome 15.
Figure 3. Gene location, Exon, Intron of drug metabolizing gene CYP2B6 located on human chromosome 19.
006
Figure 4. Gene location, Exon, Intron of drug metabolizing gene (A) CYP2C8, (B) CYP2C9 and (C) CYP2C19 located on human chromosome 10.
007
Figure 5. Gene location, Exon, Intron of drug metabolizing gene CYP3A4 located on human chromosome 7.
Figure 6. Gene location, Exon, Intron of drug metabolizing gene NAT2 located on human chromosome 7.
antimalarial
usage
lies
in
With the availability of human genome sequence, interindividual variation with respect to drug response has
become clear (Brockmoller and Tzevtkov, 2008) and
helped in understanding the fact that not all individual can
008
ACKNOWLEDGEMENT
The authors wish to thanks the Indian Council of Medical
Research (ICMR) for Junior and Senior Research
Fellowships.
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