Limited genetic variation in the Plasmodium falciparum heme detoxification protein (HDP).

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases
Sumiti VinayakVenkatachalam Udhayakumar

Abstract

Malaria parasites infecting host red blood cells degrade hemoglobin by detoxifying heme into hemozoin. This conversion of heme to hemozoin is performed by a potent protein called heme detoxification protein (HDP), making HDP an attractive target for antimalarial drug development. We studied the genetic variation in Plasmodium falciparum HDP and also investigated if HDP due to its involvement in the heme detoxification pathway is under any potential chloroquine (CQ) selection pressure. We sequenced the complete HDP gene encompassing three exons and two introns (AT and ATTT repeats in intron 1; AT repeats in intron 2) from five P. falciparum laboratory strains with known CQ sensitivity and 50 field isolates from Venezuela (n=26) and Kenya (n=24), with high levels of CQ resistance. Sequencing revealed two mutations, C41F and F91L in exon 1 and exon 2, respectively. The F41 mutation was present only in the CQ sensitive (CQS) HB3 strain. However, all the isolates harbored the 91L mutation, except for the CQS 3D7 strain. The sequencing of the intron 2 region revealed no variation in the number of AT repeats. In contrast, there was a wide variation in the AT and ATTT repeats in intron 1. Overall with respect to the intron 1 repeats, t...Continue Reading

References

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Citations

Dec 3, 2015·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Suthat PhaiphinitKitiporn Plaimas
Sep 21, 2013·Journal of Medical Microbiology·Joel C Mouatcho, J P Dean Goldring
Sep 13, 2013·Biochemical and Biophysical Research Communications·Keisuke NakataniYasuhisa Mizutani

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