Associations of Single Nucleotide Polymorphisms in IL-18 Gene with Plasmodium falciparum-Associated Malaria

Alaa U AlRuwaisan,1 Mashael R Al-Anazi,2 Mohammed I Shafeai,3 Fuad H Rudiny,3 Ali M Motaen,3 Saad M Bin Dajem,4 Hani Alothaid,5 Kareem Morsy,4,6 Saad Alkahtani,1 Ahmed A Al-Qahtani2,7 1Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia; 2Department of Infection and Im...

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Autores principales:	AlRuwaisan AU, Al-Anazi MR, Shafeai MI, Rudiny FH, Motaen AM, Bin Dajem SM, Alothaid H, Morsy K, Alkahtani S, Al-Qahtani AA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	plasmodium falciparum il-18 gene snps Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/ce22b3b274954acd96b623d2edb250e8
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spelling	oai:doaj.org-article:ce22b3b274954acd96b623d2edb250e82021-12-02T18:41:58ZAssociations of Single Nucleotide Polymorphisms in IL-18 Gene with Plasmodium falciparum-Associated Malaria1178-7031https://doaj.org/article/ce22b3b274954acd96b623d2edb250e82021-07-01T00:00:00Zhttps://www.dovepress.com/associations-of-single-nucleotide-polymorphisms-in-il-18-gene-with-pla-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Alaa U AlRuwaisan,1 Mashael R Al-Anazi,2 Mohammed I Shafeai,3 Fuad H Rudiny,3 Ali M Motaen,3 Saad M Bin Dajem,4 Hani Alothaid,5 Kareem Morsy,4,6 Saad Alkahtani,1 Ahmed A Al-Qahtani2,7 1Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia; 2Department of Infection and Immunity, Research Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia; 3Sabya General Hospital, Sabya, Saudi Arabia; 4Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia; 5Department of Basic Sciences, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha, Saudi Arabia; 6Zoology Department, Faculty of Science, Cairo University, Cairo, Egypt; 7Department of Microbiology and Immunology, College of Medicine, Alfaisal University, Riyadh, Saudi ArabiaCorrespondence: Ahmed A Al-Qahtani Email aqahtani@kfshrc.edu.saIntroduction: Interleukin-18 (IL-18) is a pro-inflammatory cytokine, reported to be involved in the initial immune responses against malaria. Genetic variations in the host are an important factor that influences the etiology of malaria at several disease levels. Polymorphisms within the IL-18 gene are associated with susceptibility and clinical outcome of several diseases.Methods: We genotyped single nucleotide polymorphisms (SNPs) in IL-18 of patients infected with Plasmodium falciparum with varying extent of parasitemia and different age groups.Results: SNPs rs5744292 (OR = 70.446; 95% CI = 4.318– 1149.323; p< 0.0001) and rs544354 (OR = 1.498; 95% CI = 1.088– 2.063; p=0.013) were found to be significantly associated with parasitemia in P. falciparum-infected patients when compared with healthy control subjects. SNP rs5744292 (OR = 7.597; 95% CI=1.028– 56.156; p=0.019) was associated with increased parasite density in infected patients. SNPs rs544354 (OR 0.407; 95% CI=0.204– 0.812; p = 0.009) and rs360714 (OR of 0.256; 95% CI=0.119– 0.554; p = 0.001) were significantly associated with parasite density in an age-dependent manner, with the risk alleles present more frequently among the younger (1– 9 years) patients. Several haplotypes were found to have a significant association with parasitemia. In-vitro expression analysis using luciferase reporter assay showed that SNPs rs1946518 and rs187238 in the IL-18 gene promoter region and rs360728 and rs5744292 in the 3ʹ-untranslated region of the IL-18 gene were associated with enhanced transcriptional activity.Conclusion: Our results suggest that polymorphisms within the IL-18 gene are associated with the susceptibility to P. falciparum infection and related parasitemia among groups with different parasite density and across various age groups.Keywords: Plasmodium falciparum, IL-18 gene, SNPsAlRuwaisan AUAl-Anazi MRShafeai MIRudiny FHMotaen AMBin Dajem SMAlothaid HMorsy KAlkahtani SAl-Qahtani AADove Medical Pressarticleplasmodium falciparumil-18 genesnpsPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 3587-3619 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	plasmodium falciparum il-18 gene snps Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	plasmodium falciparum il-18 gene snps Pathology RB1-214 Therapeutics. Pharmacology RM1-950 AlRuwaisan AU Al-Anazi MR Shafeai MI Rudiny FH Motaen AM Bin Dajem SM Alothaid H Morsy K Alkahtani S Al-Qahtani AA Associations of Single Nucleotide Polymorphisms in IL-18 Gene with Plasmodium falciparum-Associated Malaria
description	Alaa U AlRuwaisan,1 Mashael R Al-Anazi,2 Mohammed I Shafeai,3 Fuad H Rudiny,3 Ali M Motaen,3 Saad M Bin Dajem,4 Hani Alothaid,5 Kareem Morsy,4,6 Saad Alkahtani,1 Ahmed A Al-Qahtani2,7 1Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia; 2Department of Infection and Immunity, Research Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia; 3Sabya General Hospital, Sabya, Saudi Arabia; 4Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia; 5Department of Basic Sciences, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha, Saudi Arabia; 6Zoology Department, Faculty of Science, Cairo University, Cairo, Egypt; 7Department of Microbiology and Immunology, College of Medicine, Alfaisal University, Riyadh, Saudi ArabiaCorrespondence: Ahmed A Al-Qahtani Email aqahtani@kfshrc.edu.saIntroduction: Interleukin-18 (IL-18) is a pro-inflammatory cytokine, reported to be involved in the initial immune responses against malaria. Genetic variations in the host are an important factor that influences the etiology of malaria at several disease levels. Polymorphisms within the IL-18 gene are associated with susceptibility and clinical outcome of several diseases.Methods: We genotyped single nucleotide polymorphisms (SNPs) in IL-18 of patients infected with Plasmodium falciparum with varying extent of parasitemia and different age groups.Results: SNPs rs5744292 (OR = 70.446; 95% CI = 4.318– 1149.323; p< 0.0001) and rs544354 (OR = 1.498; 95% CI = 1.088– 2.063; p=0.013) were found to be significantly associated with parasitemia in P. falciparum-infected patients when compared with healthy control subjects. SNP rs5744292 (OR = 7.597; 95% CI=1.028– 56.156; p=0.019) was associated with increased parasite density in infected patients. SNPs rs544354 (OR 0.407; 95% CI=0.204– 0.812; p = 0.009) and rs360714 (OR of 0.256; 95% CI=0.119– 0.554; p = 0.001) were significantly associated with parasite density in an age-dependent manner, with the risk alleles present more frequently among the younger (1– 9 years) patients. Several haplotypes were found to have a significant association with parasitemia. In-vitro expression analysis using luciferase reporter assay showed that SNPs rs1946518 and rs187238 in the IL-18 gene promoter region and rs360728 and rs5744292 in the 3ʹ-untranslated region of the IL-18 gene were associated with enhanced transcriptional activity.Conclusion: Our results suggest that polymorphisms within the IL-18 gene are associated with the susceptibility to P. falciparum infection and related parasitemia among groups with different parasite density and across various age groups.Keywords: Plasmodium falciparum, IL-18 gene, SNPs
format	article
author	AlRuwaisan AU Al-Anazi MR Shafeai MI Rudiny FH Motaen AM Bin Dajem SM Alothaid H Morsy K Alkahtani S Al-Qahtani AA
author_facet	AlRuwaisan AU Al-Anazi MR Shafeai MI Rudiny FH Motaen AM Bin Dajem SM Alothaid H Morsy K Alkahtani S Al-Qahtani AA
author_sort	AlRuwaisan AU
title	Associations of Single Nucleotide Polymorphisms in IL-18 Gene with Plasmodium falciparum-Associated Malaria
title_short	Associations of Single Nucleotide Polymorphisms in IL-18 Gene with Plasmodium falciparum-Associated Malaria
title_full	Associations of Single Nucleotide Polymorphisms in IL-18 Gene with Plasmodium falciparum-Associated Malaria
title_fullStr	Associations of Single Nucleotide Polymorphisms in IL-18 Gene with Plasmodium falciparum-Associated Malaria
title_full_unstemmed	Associations of Single Nucleotide Polymorphisms in IL-18 Gene with Plasmodium falciparum-Associated Malaria
title_sort	associations of single nucleotide polymorphisms in il-18 gene with plasmodium falciparum-associated malaria
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/ce22b3b274954acd96b623d2edb250e8
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Associations of Single Nucleotide Polymorphisms in IL-18 Gene with Plasmodium falciparum-Associated Malaria

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