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. 2019 Dec 30;18(1):446.
doi: 10.1186/s12936-019-3084-4.

Genetic polymorphism of histidine rich protein 2 in Plasmodium falciparum isolates from different infection sources in Yunnan Province, China

Ying Dong  1 , Shuping Liu  2   3 , Yan Deng  2 , Yanchun Xu  2 , Mengni Chen  2 , Yan Liu  2 , Jingpo Xue  4
Affiliations

Genetic polymorphism of histidine rich protein 2 in Plasmodium falciparum isolates from different infection sources in Yunnan Province, China

Ying Dong et al. Malar J. .

Abstract

Background: Failed diagnoses of some falciparum malaria cases by RDTs are constantly reported in recent years. Plasmodium falciparum histidine-rich protein 2 (pfhpr2) gene deficiency has been found to be the major reason of RDTs failure in many countries. This article analysed the deletion of pfhpr2 gene of falciparum malaria cases isolated in Yunnan Province, China.

Methods: Blood samples from falciparum malaria cases diagnosed in Yunnan Province were collected. Plasmodium genomic DNA was extracted and the pfhrp2 gene exon2 region was amplified via nested PCR. The haplotype of the DNA sequence, the nucleic acid diversity index (PI) and expected heterozygosity (He) were analyzed. Count PfHRP2 amino acid peptide sequence repeat and its times, and predict the properties of PfHRP2 peptide chain reaction to RDTs testing.

Results: A total of 306 blood samples were collected, 84.9% (259/306) from which pfhrp2 PCR amplification products (gene exon2) were obtained, while the remaining 47 samples were false amplification. The length of the 250 DNA sequences ranged from 345 - 927 bp, with 151 haplotypes, with PI and He values of 0.169 and 0.983, respectively. The length of the PfHRP2 peptide chain translated from 250 DNA sequences ranged from 115 to 309 aa. All peptide chains had more than an amino acid codon deletion. All 250 PfHRP2 strands ended with a type 12 amino acid repeat, 98.0% (245/250) started with a type 1 repetition and 2.0% (5/250) with a type 2 repetition. The detection rate for type 2 duplicates was 100% (250/250). Prediction of RDT sensitivity of PfHRP2 peptide chains based on type 2 and type 7 repeats showed that 9.60% (24/250), 50.0% (125/250), 13.20% (33/250) and 27.20.5% (68/250) of the 250 peptide chains were very sensitive, sensitive, borderline and non-sensitive, respectively.

Conclusion: The diversified polymorphism of the pfhrp2 gene deletion from different infection sources in the Yunnan province are extremely complex. The cause of the failure of pfhrp2 exon2 amplification is still to be investigated. The results of this study appeal to Yunnan Province for a timely evaluation of the effectiveness and applicability of RDTs in the diagnosis of malaria.

Keywords: Deletion polymorphism; Different infection sources; Histidine-rich protein 2; Peptid chain; Plasmodium falciparum; Yunnan.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Distribution of falciparum cases blood samples including successful and unsuccessful PCR amplification of pfhrp2 gene exon2 region. (1) The different colours from dark red to light red in administrative areas represented samples with hrp2 gene. PCR amplication product that were collected from falciparum malaria cases found during study period, including Dehong, Kuming, Baoshan, Lincang, Dali, Pu’er, Qujing, Zhaotong, Nujiang, Lijiang, Xishuangbanna, Weishan, Honghe, Yuxi and Chuxiong –15 prefectures in Yunnan Province; White range indicates no falciparum malaria cases found during study period in this prefecture (only one) which is Diqing in Yunnan Province. (2) Pie charts represented failed amplification of samples with hrp2 gene PCR. They were found in Dehong, Baoshan, Kuming, Dali, Lincang, Pu’er and Qujing 7 prefectures in Yunnan Province
Fig. 2
Fig. 2
Alignment mapping of amino acid chains from different haplotypes. The alignment reference sequence was PF3D7_0831800. The alignment region of amino acid chain was from 57th to 301th aa in pfhrp2 gene exon2 region
Fig. 3
Fig. 3
PCA scatter plots of DNA sequences haplotypes of hrp2 exon2 region from different infection source P. falciparum isolates. (1) The horizontal yellow line was the X axis, and vertical yellow line the Y axis, and left inclined yellow line the Z axis. (2) The different color blocks represented haplotypes, in which yellow blocks were these haplotypes with the minimum PCA value and red blocks were those with the maximum PCA value. (3) The number labels on the block were the haplotype names with frequencies greater than 0.8%. A labels block are haplotypes with only sequence of African isolates, and Y labels block are haplotypes with only sequence of Yunnan Province local isolates, and no labels block are haplotypes with only sequence of Myanmar isolates
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