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Host susceptibility genes of asymptomatic malaria from South Central Timor, Eastern Indonesia

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Abstract

Host genetic factors, such as the genes for various cytokines and adhesion molecules, play a significant role in determining susceptibility to malaria infection. Polymorphisms in host genes have been correlated with malaria infection in both African and Asian regions. The purpose of this study was to investigate the association between both cytokine and adhesion molecule genotypes with susceptibility to malaria infection in humans. Ten cytokine polymorphism loci (IL4 + 33, IL4-590, IL6-174, IL10-1082, IL10-1035, IL12p40, TNF-238, TNF-308, TNF-1031, and TNF-β) and three adhesion molecule polymorphism loci (CD36 exon 10, ICAM-1 Kilifi, and ICAM-1 exon 6) were genotyped using PCR–RFLP analysis. We conducted this study on 178 asymptomatic malaria subjects and 122 uninfected subjects. Results showed that certain CD36 exon 10 and IL10-3575 polymorphisms were associated with asymptomatic infection. The heterozygous (GT) and homozygous (GG) genotypes for CD36 exon 10 are associated with an increased risk of malaria infection. On the other hand, the homozygous genotype (AA) for IL10-3575 reduced the risk of asymptomatic malaria infection. No significant differences were found for the other polymorphisms studied. We also found that a polymorphism in CD36 exon 10 was strongly associated with asymptomatic malaria caused specifically by Plasmodium vivax. These findings suggest that the G allele of CD36 exon 10 is associated with an increased risk of asymptomatic malaria infection. On the other hand, the genotype AA for IL10-3575 was associated with a reduced risk of malaria infection.

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Abbreviations

CD36:

Cluster of differentiation 36

HWE:

Hardy-Weinberg equilibrium

ICAM-1:

Intracellular adhesion molecule 1

IL:

Interleukin

PCR:

Polymerase chain reaction

PCR–RFLP :

Polymerase chain reaction-restriction fragment length polymorphism

P. falciparum :

Plasmodium falciparum

P. vivax :

Plasmodium vivax

TNF:

Tumor necrosis factor

WHO:

World Health Organization

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Acknowledgements

We are grateful to Dr. Phunuch Muhamad and Dr. Kridsada Sirisabhabhorn for providing positive control.

Funding

This study was jointly supported by Chulabhorn International College of Medicine, Thammasat University, Center of Excellence in Pharmacology and Malaria and Cholangiocarcinoma of Thammasat University, the National Research Council of Thailand under the Research Team Promotion grant (grant number NRCT 820/2563), and the National Institute of Health Research and Development, Ministry of the Health Republic of Indonesia. Mrs. Nyoman Fitri gratefully acknowledges the financial support provided by Thammasat University Research Fund under Thammasat University Research Scholar, Contract No. 137/2560.

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Nyoman Fiti was the principal investigator of the study and drafted the first version of the manuscript. Kesara Na-Bangchang and Wanna Chaijaroenkul designed the study and performed the data analysis and review of the manuscript. Jontari Hutagalung and Sunarno Sunarno executed the field and laboratory works. Emiliana Tjitra, Rita Marleta Dewi, and Sarwo Handayani coordinated the field operation and arrangements. All authors reviewed the manuscript, provided intellectual inputs, and approved this manuscript.

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Correspondence to Wanna Chaijaroenkul.

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Ethical approval was obtained from the Ethics Committee of the National Institute of Health Research and Development, Ministry of Health, Jakarta (EC no. LB.02.01/2/KE.319/2019). All participants consent to participate in this study.

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Fitri, N., Na-Bangchang, K., Tjitra, E. et al. Host susceptibility genes of asymptomatic malaria from South Central Timor, Eastern Indonesia. Parasitol Res 122, 61–75 (2023). https://doi.org/10.1007/s00436-022-07696-0

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