Association between polymorphisms of IL4, IL13, IL10, STAT6 and IFNG genes, cytokines and immunoglobulin E levels with high burden of Schistosoma mansoni in children from schistosomiasis endemic areas of Cameroon

Mewamba, E. M. et al. (2023) Association between polymorphisms of IL4, IL13, IL10, STAT6 and IFNG genes, cytokines and immunoglobulin E levels with high burden of Schistosoma mansoni in children from schistosomiasis endemic areas of Cameroon. Infection, Genetics and Evolution, 111, 105416. (doi: 10.1016/j.meegid.2023.105416) (PMID:36889485) (PMCID:PMC10167540)

Abstract

Eliminating schistosomiasis as a public health problem by 2030 requires a better understanding of the disease transmission, especially the asymmetric distribution of worm burden in individuals living and sharing the same environment. It is in this light that this study was designed to identify human genetic determinants associated with high burden of S. mansoni and also with the plasma concentrations of IgE and four cytokines in children from two schistosomiasis endemic areas of Cameroon. In school-aged children of schistosomiasis endemic areas of Makenene and Nom-Kandi of Cameroon, S. mansoni infections and their infection intensities were evaluated in urine and stool samples using respectively the Point-of-care Circulating Cathodic Antigen test (POC-CCA) and the Kato Katz (KK) test. Thereafter, blood samples were collected in children harbouring high burden of schistosome infections as well as in their parents and siblings. DNA extracts and plasma were obtained from blood. Polymorphisms at 14 loci of five genes were assessed using PCR-restriction fragment length polymorphism and amplification-refractory mutation system. The ELISA test enabled to determine the plasma concentrations of IgE, IL-13, IL-10, IL-4 and IFN-γ. The prevalence of S. mansoni infections was significantly higher (P < 0.0001 for POC-CCA; P = 0.001 for KK) in Makenene (48.6% for POC-CCA and 7.9% for KK) compared to Nom-Kandi (31% for POC-CCA and 4.3% for KK). The infection intensities were also higher (P < 0.0001 for POC-CCA; P = 0.001 for KK) in children from Makenene than those from Nom-Kandi. The allele C of SNP rs3024974 of STAT6 was associated with an increased risk of bearing high burden of S. mansoni both in the additive (p = 0.009) and recessive model (p = 0.01) while the allele C of SNP rs1800871 of IL10 was protective (p = 0.0009) against high burden of S. mansoni. The alleles A of SNP rs2069739 of IL13 and G of SNP rs2243283 of IL4 were associated with an increased risk of having low plasma concentrations of IL-13 (P = 0.04) and IL-10 (P = 0.04), respectively. This study showed that host genetic polymorphisms may influence the outcome (high or low worm burden) of S. mansoni infections and also the plasma concentrations of some cytokines.

• Item Type: Articles
• Additional Information: Funding: This work was funded through the Human Heredity and Health in Africa (H3Africa; Grant ID H3A-18-004) from the Science for Africa Foundation. H3Africa is jointly supported by Wellcome and the National Institutes of Health (NIH). We acknowledge additional support from the Royal Society of Tropical Medicine and Hygiene (RSTMH) small grant 2021 (to EMM, Membership No. 0021514) who funded through the National Institute for Health Research (NIHR). The NIHR is a major funder of high-quality research that directly addresses the diverse health needs of people in low- and middle-income countries (LMICs), working in collaboration with other global health leaders. This work was also funded by a grant from the United States Agency for International Development (USAID) and UK aid from the British people (UK aid) to EMM through the Coalition for Operational Research on Neglected Tropical Diseases (COR-NTD) and administered by the African Research Network for Neglected Tropical Diseases (ARNTD); grant number SGPIII/0210/388.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: MacLeod, Professor Annette
• Authors: Mewamba, E. M., Noyes, H., Tiofack, A. A. Z., Kamga, R. M. N., Kamdem, C. N., Mengoue, L. E. T., Ofon, E., Ngassam, R. I. K., Nyangiri, O., Bucheton, B., Njiokou, F., Womeni, M. H., Matovu, E., MacLeod, A., and Simo, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Infection, Genetics and Evolution
• Publisher: Elsevier
• ISSN: 1567-1348
• ISSN (Online): 1567-7257
• Published Online: 06 March 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Infection, Genetics and Evolution 11:105416
• Publisher Policy: Reproduced under a Creative Commons license