Genetic diversity of the Duffy antigen/receptor for chemokines gene and its susceptibility to zoonotic malaria in non-human primates and Indonesian populations

Background and Aim: Zoonotic malaria caused by Plasmodium knowlesi presents a growing public health challenge in Southeast Asia. Host genetic factors, particularly polymorphisms in the Duffy antigen/receptor for chemokines (DARC), may influence susceptibility to zoonotic transmission. Indonesia’s va...

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Main Authors: Dendi H. Permana, Puji B. S. Asih, Dwi A. Suryandari, Elsa H. Murhandarwati, Isfanda Isfanda, Ismail E. Rozi, Lepa Syahrani, Farah N. Coutrier, Hannie Kartapradja, Hairul Afzan, Najdah Hidayah, Din Syafruddin
Format: Article
Language:English
Published: Veterinary World 2025-05-01
Series:International Journal of One Health
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Online Access:https://onehealthjournal.org/Vol.11/No.1/14.pdf
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author Dendi H. Permana
Puji B. S. Asih
Dwi A. Suryandari
Elsa H. Murhandarwati
Isfanda Isfanda
Ismail E. Rozi
Lepa Syahrani
Farah N. Coutrier
Hannie Kartapradja
Hairul Afzan
Najdah Hidayah
Din Syafruddin
author_facet Dendi H. Permana
Puji B. S. Asih
Dwi A. Suryandari
Elsa H. Murhandarwati
Isfanda Isfanda
Ismail E. Rozi
Lepa Syahrani
Farah N. Coutrier
Hannie Kartapradja
Hairul Afzan
Najdah Hidayah
Din Syafruddin
author_sort Dendi H. Permana
collection DOAJ
description Background and Aim: Zoonotic malaria caused by Plasmodium knowlesi presents a growing public health challenge in Southeast Asia. Host genetic factors, particularly polymorphisms in the Duffy antigen/receptor for chemokines (DARC), may influence susceptibility to zoonotic transmission. Indonesia’s vast ethnic and ecological diversity offers a unique context to explore the genetic interface between human and non-human primate (NHP) hosts and zoonotic malaria. This study aimed to investigate the genetic diversity of the DARC gene in sympatric human and NHP populations across Indonesia and its potential role in modulating susceptibility to zoonotic malaria. Materials and Methods: A cross-sectional survey was conducted in Sabang (Aceh), Palangkaraya (Central Kalimantan), and North Buton (Southeast Sulawesi). Dried blood spots were collected from 68 NHPs and 363 humans. DARC promoter and coding regions were amplified through polymerase chain reaction, sequenced, and analyzed using bioinformatic tools. Phylogenetic analyses and allele-specific comparisons were performed to assess cross-species genetic similarity and regional variation in DARC alleles. Results: No −46T>C promoter single-nucleotide polymorphism associated with Duffy negativity was found in either humans or NHPs. Three genotypic forms – FYA, FYB, and FYA/FYB – were observed in human populations, with FYA being predominant in Kalimantan and Sulawesi. Notably, individuals with the FYA allele in Aceh, a region with high P. knowlesi incidence, were less likely to have an infection, suggesting a potential protective role. All NHPs carried the FY*B allele. Comparative analyses revealed high DARC sequence homology between humans and NHPs, particularly Macaca fascicularis and Macaca brunnescens, implicating molecular compatibility in zoonotic transmission dynamics. Conclusion: This is the first comprehensive study to assess DARC gene polymorphisms in both human and NHP populations in Indonesia within the context of zoonotic malaria. The findings underscore the significance of host genetic variation in mediating susceptibility to P. knowlesi and highlight regional allele profiles as potential markers for risk stratification. These insights provide a genomic framework to inform surveillance and control strategies in malaria-endemic regions vulnerable to zoonotic transmission.
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spelling doaj-art-ddb1ca22e82e44e08945605edc76142e2025-08-20T03:12:46ZengVeterinary WorldInternational Journal of One Health2455-56732455-89312025-05-0111114715810.14202/IJOH.2025.147-158Genetic diversity of the Duffy antigen/receptor for chemokines gene and its susceptibility to zoonotic malaria in non-human primates and Indonesian populationsDendi H. Permana0https://orcid.org/0000-0003-3002-1008Puji B. S. Asih1https://orcid.org/0000-0002-4582-9133Dwi A. Suryandari2https://orcid.org/0000-0003-2711-8335Elsa H. Murhandarwati3https://orcid.org/0000-0002-0374-8167Isfanda Isfanda4https://orcid.org/0000-0002-2382-1317Ismail E. Rozi5https://orcid.org/0000-0003-4930-5123Lepa Syahrani6https://orcid.org/0000-0002-3126-1743Farah N. Coutrier7https://orcid.org/0000-0003-3141-0697Hannie Kartapradja8https://orcid.org/0000-0002-6465-7349Hairul Afzan9https://orcid.org/0009-0005-6243-129XNajdah Hidayah10https://orcid.org/0000-0002-9811-2080Din Syafruddin11https://orcid.org/0000-0001-7141-2545Doctoral Program in Biomedical Science, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia; Eijkman Research Center for Molecular Biology, National Research and Innovation Agency, Cibinong, Indonesia.Eijkman Research Center for Molecular Biology, National Research and Innovation Agency, Cibinong, Indonesia.Department of Biology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.Center for Tropical Medicine, Faculty of Medicine, Public Health, and Nursing, University of Gadjah Mada, Yogyakarta, Indonesia; Department of Parasitology, Faculty of Medicine, Public Health, and Nursing, University of Gadjah Mada, Yogyakarta, Indonesia.Doctoral Program in Medicine, University of Syiah Kuala, Aceh, Indonesia; Medical Program, Faculty of Medicine, University of Abulyatama, Aceh, Indonesia.Eijkman Research Center for Molecular Biology, National Research and Innovation Agency, Cibinong, Indonesia; Doctoral Program in Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.Eijkman Research Center for Molecular Biology, National Research and Innovation Agency, Cibinong, Indonesia; Doctoral Program in Faculty of Mathematics and Natural Sciences, University of Indonesia, Depok, Indonesia.Eijkman Research Center for Molecular Biology, National Research and Innovation Agency, Cibinong, Indonesia.Eijkman Research Center for Molecular Biology, National Research and Innovation Agency, Cibinong, Indonesia.Malaria and Vector Resistance Laboratory, Hasanuddin University Medical Research Center, Makassar, Indonesia.Malaria and Vector Resistance Laboratory, Hasanuddin University Medical Research Center, Makassar, Indonesia.Malaria and Vector Resistance Laboratory, Hasanuddin University Medical Research Center, Makassar, Indonesia; Department of Parasitology, Faculty of Medicine, University of Hasanuddin, Makassar, Indonesia.Background and Aim: Zoonotic malaria caused by Plasmodium knowlesi presents a growing public health challenge in Southeast Asia. Host genetic factors, particularly polymorphisms in the Duffy antigen/receptor for chemokines (DARC), may influence susceptibility to zoonotic transmission. Indonesia’s vast ethnic and ecological diversity offers a unique context to explore the genetic interface between human and non-human primate (NHP) hosts and zoonotic malaria. This study aimed to investigate the genetic diversity of the DARC gene in sympatric human and NHP populations across Indonesia and its potential role in modulating susceptibility to zoonotic malaria. Materials and Methods: A cross-sectional survey was conducted in Sabang (Aceh), Palangkaraya (Central Kalimantan), and North Buton (Southeast Sulawesi). Dried blood spots were collected from 68 NHPs and 363 humans. DARC promoter and coding regions were amplified through polymerase chain reaction, sequenced, and analyzed using bioinformatic tools. Phylogenetic analyses and allele-specific comparisons were performed to assess cross-species genetic similarity and regional variation in DARC alleles. Results: No −46T>C promoter single-nucleotide polymorphism associated with Duffy negativity was found in either humans or NHPs. Three genotypic forms – FYA, FYB, and FYA/FYB – were observed in human populations, with FYA being predominant in Kalimantan and Sulawesi. Notably, individuals with the FYA allele in Aceh, a region with high P. knowlesi incidence, were less likely to have an infection, suggesting a potential protective role. All NHPs carried the FY*B allele. Comparative analyses revealed high DARC sequence homology between humans and NHPs, particularly Macaca fascicularis and Macaca brunnescens, implicating molecular compatibility in zoonotic transmission dynamics. Conclusion: This is the first comprehensive study to assess DARC gene polymorphisms in both human and NHP populations in Indonesia within the context of zoonotic malaria. The findings underscore the significance of host genetic variation in mediating susceptibility to P. knowlesi and highlight regional allele profiles as potential markers for risk stratification. These insights provide a genomic framework to inform surveillance and control strategies in malaria-endemic regions vulnerable to zoonotic transmission.https://onehealthjournal.org/Vol.11/No.1/14.pdfdarc genegenetic polymorphismhost-pathogen interactionindonesiamalaria susceptibilitynonhuman primatesplasmodium knowlesizoonotic malaria
spellingShingle Dendi H. Permana
Puji B. S. Asih
Dwi A. Suryandari
Elsa H. Murhandarwati
Isfanda Isfanda
Ismail E. Rozi
Lepa Syahrani
Farah N. Coutrier
Hannie Kartapradja
Hairul Afzan
Najdah Hidayah
Din Syafruddin
Genetic diversity of the Duffy antigen/receptor for chemokines gene and its susceptibility to zoonotic malaria in non-human primates and Indonesian populations
International Journal of One Health
darc gene
genetic polymorphism
host-pathogen interaction
indonesia
malaria susceptibility
nonhuman primates
plasmodium knowlesi
zoonotic malaria
title Genetic diversity of the Duffy antigen/receptor for chemokines gene and its susceptibility to zoonotic malaria in non-human primates and Indonesian populations
title_full Genetic diversity of the Duffy antigen/receptor for chemokines gene and its susceptibility to zoonotic malaria in non-human primates and Indonesian populations
title_fullStr Genetic diversity of the Duffy antigen/receptor for chemokines gene and its susceptibility to zoonotic malaria in non-human primates and Indonesian populations
title_full_unstemmed Genetic diversity of the Duffy antigen/receptor for chemokines gene and its susceptibility to zoonotic malaria in non-human primates and Indonesian populations
title_short Genetic diversity of the Duffy antigen/receptor for chemokines gene and its susceptibility to zoonotic malaria in non-human primates and Indonesian populations
title_sort genetic diversity of the duffy antigen receptor for chemokines gene and its susceptibility to zoonotic malaria in non human primates and indonesian populations
topic darc gene
genetic polymorphism
host-pathogen interaction
indonesia
malaria susceptibility
nonhuman primates
plasmodium knowlesi
zoonotic malaria
url https://onehealthjournal.org/Vol.11/No.1/14.pdf
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