Genetic polymorphism at the C-terminal domain (region III) of knob-associated histidine-rich protein (KAHRP) of Plasmodium falciparum in isolates from Iran

Abstract

The knob-associated histidine-rich protein (KAHRP) plays a major role in the virulence of Plasmodium falciparum and is one of the targets for molecular therapy. The primary structure of KAHRP of P. falciparum consists of three domains (regions I-III), of which the C-terminal domain (region III) is the most polymorphic segment of this protein. One of the main obstacles is genetic diversity in designing and developing of malaria control strategies such as molecular therapy and vaccines. The primary objective of the present study was to investigate and analyze the extent of genetic polymorphism at the region III of KAHRP of P. falciparum in isolates from Iran. A fragment of the kahrp gene spanning the C-terminal domain was amplified by nested PCR from 50 P. falciparum isolates collected from two malaria endemic areas of Iran during 2009 to August 2010 and sequenced. In this study, three allelic types were observed at the C-terminal domain of KAHRP on the basis of the molecular weight of nested PCR products and the obtained sequencing data. The presence of multiple alleles of the kahrp gene indicates that several P. falciparum strains exist in the malaria endemic areas of Iran. Our findings will be valuable in the design and the development of the molecular therapeutic reagents for falciparum malaria.

Genetic diversity at the C-terminal domain of knob-associated histidine-rich protein (KAHRP) of Plasmodium falciparum isolates from Burundi, Eastern Africa

“…The results of our study revealed that the region III of the kahrp gene was polymorphic, as it had been already showed [13,15,16,20]. The existence of multiple allelic forms of the kahrp gene identified the presence of different P. falciparum strains in Burundi.…”

“…3). Moreover, according to the BLAST homology searches and phylogenetic analysis results of this study and a previous study conducted in Iran [20], it is appear that the Iranian P. falciparum parasites originates from Africa. Thus, further epidemiological and molecular investigations will help us to clear the hypothesis.…”

“…Like the previous study performed in Iran [20], the type III (400 bp) allele was predominant (23/35, 65.71%) in the 35 Burundian P. falciparum isolates and their molecular weight was the same size as NF7-Ghana, Pf3-92 from India, and 26 Iranian P. falciparum isolates [8,19,20]. The isolates with 370 bp allele were identical to the HB3-Honduras, Indian RJ181, and 20 isolates from Iran.…”

“…The isolates with 370 bp allele were identical to the HB3-Honduras, Indian RJ181, and 20 isolates from Iran. The phenotype of the low molecular weight alleles (340 bp) was similar to the FCR3-Gambia, Pf 29-92 from Indian, and the three isolates of Iran [19,20]. …”

“…As the PfHRP-1 is one of the molecular therapy targets, the reagents that inhibit the formation of knobs will be effective in the treatment of severe malaria [18]. Although the polymorphism of PfHRP-1 investigated in several malaria endemic areas [[14], [15], [16],19,20], the present research is the first study which was conducted in Burundi, Eastern Africa. The aim of the present study was to explore the genetic diversity of region III of KAHRP in P. falciparum isolates from Burundi and compare the distribution frequency of PfHRP-1 alleles in the country.…”