Hostname: page-component-586b7cd67f-l7hp2 Total loading time: 0 Render date: 2024-11-24T08:12:25.590Z Has data issue: false hasContentIssue false
  • English
  • Français

Plasmodium falciparum: linkage disequilibrium between loci in chromosomes 7 and 5 and chloroquine selective pressure in Northern Nigeria

Published online by Cambridge University Press:  28 November 2001

I. S. ADAGU  and
D. C. WARHURST
I. S. ADAGU
Affiliation:
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WCIE 7HT, UK
D. C. WARHURST
Affiliation:
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WCIE 7HT, UK
Get access Rights & Permissions [Opens in a new window]

Abstract

In view of the recent discovery (Molecular Cell6, 861–871) of a (Lys76Thr) codon change in gene pfcrt on chromosome 7 which determines in vitro chloroquine resistance in Plasmodium falciparum, we have re-examined samples taken before treatment in our study in Zaria, Northern Nigeria (Parasitology119, 343–348). Drug resistance was present in 5/5 cases where the pfcrt 76Thr codon change was seen (100% positive predictive value). Drug sensitivity was found in 26/28 cases where the change was absent (93% negative predictive value). Allele pfcrt 76Thr showed strong linkage disequilibrium with pfmdr1 Tyr86 on chromosome 5, more complete than that between pfcrt and cg2 alleles situated between recombination cross-over points on chromosome 7. Physical linkage of cg2 with pfcrt may account for linkage disequilibrium between their alleles but in the case of genes pfmdr1 and pfcrt, on different chromosomes, it is likely that this is maintained epistatically through the selective pressure of chloroquine.

Keywords

linkage disequilibriumPlasmodium falciparumchloroquine resistancemalariaNigeria
Type
Research Article
Information
Parasitology , Volume 123 , Issue 3 , March 2001 , pp. 219 - 224
Copyright
© 2002 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

ADAGU, I. S. & WARHURST, D. C. (1999). Association of cg2 and pfmdr1 genotype with chloroquine resistance in field samples of Plasmodium falciparum from Nigeria. Parasitology 119, 343–348.CrossRefGoogle Scholar
ADAGU, I. S., WARHURST, D. C., OGALA, W. N., ABDU-AGUYE, I., AUDU, L. I., BAMGBOLA, F. O. & OVWIGHO, U. B. (1995). Antimalarial drug response of Plasmodium falciparum from Zaria, Nigeria. Transactions of the Royal Society of Tropical Medicine and Hygiene 89, 422–425.CrossRefGoogle Scholar
ADAGU, I. S., DIAS, F., PINHEIRO, L., ROMBO, L., DOROSARIO, V. & WARHURST, D. C. (1996). Guinea Bissau: association of chloroquine-resistance of Plasmodium falciparum with the Tyr86 allele of the multiple drug resistance gene Pfmdr1. Transactions of the Royal Society of Tropical Medicine and Hygiene 90, 90–91.CrossRefGoogle Scholar
AWAD-EL-KARIEM, F. M., MILES, M. A. & WARHURST, D. C. (1992). Chloroquine-resistant Plasmodium falciparum isolates from the Sudan lack two mutations in the pfmdr1 gene thought to be associated with chloroquine resistance. Transactions of the Royal Society of Tropical Medicine and Hygiene 86, 578–589.CrossRefGoogle Scholar
BASCO, L. K., LE BRAS, J., RHOADES, Z. & WILSON, C. M. (1995). Analysis of pfmdr1 and drug susceptibility in fresh isolates of Plasmodium falciparum from sub-Saharan Africa. Molecular and Biochemical Parasitology 74, 157–166.CrossRefGoogle Scholar
COWMAN, A. F., KARCZ, S., GALATIS, D. & CULVENOR, J. G. (1991). A P-glycoprotein homologue of Plasmodium falciparum is localised on the digestive vacuole. Journal of Cell Biology 113, 1033–1042.CrossRefGoogle Scholar
DJIMDE, A., DOUMBO, O. K., CORTESE, J. F., KAYENTAO, K., DOUMBO, S., DIOURTE, Y., COULIBALY, D., DICKO, A., SU, X., FIDOCK, D. A., NOMURA, T. & WELLEMS, T. E. (2001). A molecular marker for chloroquine resistant falciparum malaria. New England Journal of Medicine 344, 257–263.CrossRefGoogle Scholar
DURAISINGH, M. T., DRAKELEY, C. J., MULLER, O., BAILEY, R., SNOUNOU, G., TARGETT, G. A. T., GREENWOOD, B. M. & WARHURST, D. C. (1997). Evidence for selection for the tyrosine-86 allele of the pfmdr1 gene in Plasmodium falciparum by chloroquine and amodiaquine. Parasitology 114, 205–211.CrossRefGoogle Scholar
DURAISINGH, M. T., VON SEIDLEIN, L. V., JEPSON, A., JONES, P., SAMBOU, I., PINDER, M. & WARHURST, D. C. (2000). Linkage disequilibrium between two chromosomally distinct loci associated with increased resistance to chloroquine in Plasmodium falciparum. Parasitology 121, 1–7.CrossRefGoogle Scholar
EGGLESON, K. K., DUFFIN, K. L. & GOLDBERG, D. E. (1999). Identification and characterization of Falcilysin, a metallopeptidase involved in hemoglobin catabolism within the malaria parasite Plasmodium falciparum. Journal of Biological Chemistry 274, 32411–32417.CrossRefGoogle Scholar
FIDOCK, D. A., NOMURA, T., COOPER, R. A., SU, X., TALLEY, A. K. & WELLEMS, T. E. (2000a). Allelic modifications of the cg2 and cg1 genes do not alter the chloroquine response of the drug-resistant Plasmodium falciparum. Molecular and Biochemical Parasitology 110, 1–10.Google Scholar
FIDOCK, D. A., NOMURA, T., TALLEY, A. K., COOPER, R. A., DZEKUNOV, S. M., FERDIG, M. T., URSOS, L. M. B., SIDHU, A. S., NAUDE, B., DEITSCH, K. W., SU, X., WOOTTON, J. C., ROEPE, P. D. & WELLEMS, T. E. (2000b). Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Molecular Cell 6, 861–871.Google Scholar
FOOTE, S. J., KYLE, D. J., MARTIN, S. K., ODUOLA, A. M. J., FORSYTH, K., KEMP, D. J. & COWMAN, A. F. (1990). Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum. Nature, London 345, 255–258.CrossRefGoogle Scholar
GROBUSCH, M. P., ADAGU, I. S., KREMSNER, P. G. & WARHURST, D. C. (1998). Plasmodium falciparum: in vitro chloroquine susceptibility and allele specific PCR detection of pfmdr1Asn86Tyr polymorphism in Lambarene, Gabon. Parasitology 116, 211–217.CrossRefGoogle Scholar
HILL, W. G. & ROBERTSON, A. (1968). The effects of inbreeding at loci with heterozygote disadvantage. Genetics 60, 615–628.Google Scholar
MAYNARD SMITH, J. (1989). Evolutionary Genetics. Oxford University Press, Oxford.
PETERS, W. (1998). Drug resistance in malaria parasites of animals and man. Advances in Parasitology 41, 1–62.CrossRefGoogle Scholar
POVOA, M. M., ADAGU, I. S., OLIVEIRA, S. G., MACHADO, R. L., MILES, M. A. & WARHURST, D. C. (1998). Pfmdr1 Asn1042Asp and Asp 1246Tyr polymorphisms, thought to be associated with chloroquine resistance, are present in chloroquine-resistant and -sensitive Brazilian field isolates of Plasmodium falciparum. Experimental Parasitology 88, 64–68.CrossRefGoogle Scholar
REED, M. B, SALIBA, K. J., CARUANA, S. R., KIRK, K. & COWMAN, A. F. (2000). Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature, London 403, 906–909.CrossRefGoogle Scholar
SOKHNA, C. S., MOLEZ, J. F., NDIAYE, P., SANE, B. & TRAPE, J. F. (1997). In vivo chemosensitivity tests of Plasmodium falciparum to chloroquine in Senegal: the development of resistance and the assessment of therapeutic efficacy. Bulletin de la Société de Pathologie Exotique 90, 83–89.Google Scholar
SU, X., KIRKMAN, L. A., FUJIOKA, H. & WELLEMS, T. E. (1997). Complex polymorphisms in a ∼300 kDa protein are linked to chloroquine-resistant P. falciparum in Southeast Asia and Africa. Cell 91, 593–603.Google Scholar
SU, X., FERDIG, M. T., HUANG, Y., HUYNH, C. Q., LIU, A., YOU, J., WOOTTON, J. C. & WELLEMS, T. E. (1999). A genetic map and recombination parameters of the human malaria parasite Plasmodium falciparum. Science 286, 1351–1353.CrossRefGoogle Scholar
TRAPE, J. F., PISON, G., PREZIOSI, M. P., ENEL, C., DESGREESDU LOU, A., DELAUMAY, V., SAMB, B., LAGARDE, E., MOLEZ, J. F. & SIMONDON, F. (1998). Impact of chloroquine-resistance on malaria mortality. Comptes Rendus de l'Academie des Sciences 321, 689–697.CrossRefGoogle Scholar
WELLEMS, T. E., PANTON, L. J., GLUZMAN, I. Y., DOROSARIO, V. E., GWADZ, R. W., WALKER-JONAH, A. & KROGSTAD, D. J. (1990). Chloroquine-resistance not linked to mdr-like genes in a Plasmodium falciparum cross. Nature, London 345, 253–255.CrossRefGoogle Scholar
WELLEMS, T. E., WOOTTON, J. C., FUJIOKA, H., SU, X., COOPER, R., BARUCH, D. & FIDOCK, D. A. (1998). P. falciparum CG2, linked to chloroquine resistance, does not resemble Na+/H+ exchangers. Cell 94, 285–286.Google Scholar
WILSON, C. M., VOLKMAN, S. K., THAITHONG, S., MARTIN, R. K., KYLE, D. E., MILHOUS, W. K. & WIRTH, D. F. (1993). Amplification of pfmdr 1 associated with mefloquine and halofantrine resistance in Plasmodium falciparum from Thailand. Molecular and Biochemical Parasitology 57, 151–160.CrossRefGoogle Scholar
ZHANG, L., DRESSER, M. J., CHUN, J. K., BABBITT, P. C. & GIACOMINI, K. M. (1997). Cloning and functional characterization of a rat renal organic cation transporter isoform (rOCT1A). Journal of Biological Chemistry 272, 16548–16554.CrossRefGoogle Scholar
ZUCKER, J. R., LACKRITZ, E. M., RUEBUSH, T. K., HIGHTOWER, A. W., ADUNGOSI, J. E., WERE, J.B., METCHOCK, B., PATRICK, E. & CAMPBELL, C. C. (1996). Childhood mortality during and after hospitalization in Western Kenya: effect of malaria treatment regimes. American Journal of Tropical Medicine and Hygiene 55, 655–660.CrossRefGoogle Scholar