Association of <i>APOL1</i> renal disease risk alleles with <i>Trypanosoma brucei rhodesiense</i> infection outcomes in the northern part of Malawi



Kamoto, Kelita, Noyes, Harry ORCID: 0000-0002-0656-200X, Nambala, Peter, Senga, Edward, Musaya-Mwalija, Janelisa, Kumwenda, Benjamin, Bucheton, Bruno, Macleod, Annette, Herz-Fowler, Christiane, Matovu, Enock
et al (show 2 more authors) (2019) Association of <i>APOL1</i> renal disease risk alleles with <i>Trypanosoma brucei rhodesiense</i> infection outcomes in the northern part of Malawi. PLOS NEGLECTED TROPICAL DISEASES, 13 (8). e0007603-.

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Abstract

Trypanosoma brucei (T.b.) rhodesiense is the cause of the acute form of human African trypanosomiasis (HAT) in eastern and southern African countries. There is some evidence that there is diversity in the disease progression of T.b. rhodesiense in different countries. HAT in Malawi is associated with a chronic haemo-lymphatic stage infection compared to other countries, such as Uganda, where the disease is acute with more marked neurological impairment. This has raised the question of the role of host genetic factors in infection outcomes. A candidate gene association study was conducted in the northern region of Malawi. This was a case-control study involving 202 subjects, 70 cases and 132 controls. All individuals were from one area; born in the area and had been exposed to the risk of infection since birth. Ninety-six markers were genotyped from 17 genes: IL10, IL8, IL4, HLA-G, TNFA, IL6, IFNG, MIF, APOL, HLA-A, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH. There was a strong significant association with APOL1 G2 allele (p = 0.0000105, OR = 0.14, CI95 = [0.05-0.41], BONF = 0.00068) indicating that carriers of the G2 allele were protected against T.b. rhodesiense HAT. SNP rs2069845 in IL6 had raw p < 0.05, but did not remain significant after Bonferroni correction. There were no associations found with the other 15 candidate genes. Our finding confirms results from other studies that the G2 variant of APOL1 is associated with protection against T.b. rhodesiense HAT.

Item Type: Article
Uncontrolled Keywords: TrypanoGEN Research Group as members of The H3Africa Consortium, Humans, Trypanosoma brucei rhodesiense, Trypanosomiasis, African, Kidney Diseases, Disease Progression, Genetic Predisposition to Disease, Genetic Markers, Cytokines, Case-Control Studies, Genotype, Polymorphism, Single Nucleotide, Alleles, Adult, Middle Aged, Uganda, Malawi, Female, Male, Genetic Association Studies, Apolipoprotein L1
Depositing User: Symplectic Admin
Date Deposited: 26 May 2020 08:32
Last Modified: 09 Oct 2023 19:58
DOI: 10.1371/journal.pntd.0007603
Open Access URL: https://journals.plos.org/plosntds/article?id=10.1...
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3088573