PMID- 34345179 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220425 IS - 1178-7031 (Print) IS - 1178-7031 (Electronic) IS - 1178-7031 (Linking) VI - 14 DP - 2021 TI - Associations of Single Nucleotide Polymorphisms in IL-18 Gene with Plasmodium falciparum-Associated Malaria. PG - 3587-3619 LID - 10.2147/JIR.S314638 [doi] AB - INTRODUCTION: 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 3'-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. CI - (c) 2021 AlRuwaisan et al. FAU - AlRuwaisan, Alaa U AU - AlRuwaisan AU AD - Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia. FAU - Al-Anazi, Mashael R AU - Al-Anazi MR AD - Department of Infection and Immunity, Research Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. FAU - Shafeai, Mohammed I AU - Shafeai MI AD - Sabya General Hospital, Sabya, Saudi Arabia. FAU - Rudiny, Fuad H AU - Rudiny FH AD - Sabya General Hospital, Sabya, Saudi Arabia. FAU - Motaen, Ali M AU - Motaen AM AD - Sabya General Hospital, Sabya, Saudi Arabia. FAU - Bin Dajem, Saad M AU - Bin Dajem SM AD - Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia. FAU - Alothaid, Hani AU - Alothaid H AUID- ORCID: 0000-0003-0132-558X AD - Department of Basic Sciences, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha, Saudi Arabia. FAU - Morsy, Kareem AU - Morsy K AD - Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia. AD - Zoology Department, Faculty of Science, Cairo University, Cairo, Egypt. FAU - Alkahtani, Saad AU - Alkahtani S AUID- ORCID: 0000-0001-7381-5110 AD - Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia. FAU - Al-Qahtani, Ahmed A AU - Al-Qahtani AA AUID- ORCID: 0000-0003-4584-5739 AD - Department of Infection and Immunity, Research Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. AD - Department of Microbiology and Immunology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. LA - eng PT - Journal Article DEP - 20210726 PL - New Zealand TA - J Inflamm Res JT - Journal of inflammation research JID - 101512684 PMC - PMC8323861 OTO - NOTNLM OT - IL-18 gene OT - Plasmodium falciparum OT - SNPs COIS- The authors have nothing to declare with respect to the research, authorship, and/or publication of this article. EDAT- 2021/08/05 06:00 MHDA- 2021/08/05 06:01 PMCR- 2021/07/26 CRDT- 2021/08/04 07:04 PHST- 2021/04/07 00:00 [received] PHST- 2021/06/23 00:00 [accepted] PHST- 2021/08/04 07:04 [entrez] PHST- 2021/08/05 06:00 [pubmed] PHST- 2021/08/05 06:01 [medline] PHST- 2021/07/26 00:00 [pmc-release] AID - 314638 [pii] AID - 10.2147/JIR.S314638 [doi] PST - epublish SO - J Inflamm Res. 2021 Jul 26;14:3587-3619. doi: 10.2147/JIR.S314638. eCollection 2021.