Haptoglobin gene diversity and incidence of uncomplicated malaria among children in Iganga, Uganda
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(2020) 19:435 Lwanira et al. Malar J https://doi.org/10.1186/s12936-020-03515-y
Open Access
RESEARCH
Haptoglobin gene diversity and incidence of uncomplicated malaria among children in Iganga, Uganda Catherine N. Lwanira1,4* , Fred Kironde1,2† and Göte Swedberg3†
Abstract Background: Haptoglobin (Hp) is an acute phase protein that takes part in systemic regulation of haem during Plasmodium falciparum infections. Numerous genotypes of haptoglobin have been reported in malaria endemic populations. In this study, the relationship between haptoglobin genotypes and incidence of uncomplicated malaria in a cohort of children living in a malaria-endemic area of Uganda was determined. Methods: This is an extension of a longitudinal study comprising of 423 children aged between six months and nine years, who were actively followed up for one year. Malaria episodes occurring in the cohort children were detected and the affected children treated with national policy drug regimen. Haptoglobin genotypes were determined by an allele-specific PCR method and their frequencies were calculated. A multivariate negative binomial regression model was used to estimate the impact of haptoglobin genotypes on incidence of uncomplicated malaria in the children’s cohort. In all statistical tests, a P–value of Hp 2–1 > Hp 2–2 [7]. In earlier studies, Hp genotypes were found to be associated with altered plasma Hp levels [9, 10] and malaria outcomes [11]. The Hp 2–2 genotype that leads to lowest circulating plasma Hp levels [12] was associated with lower incidence of clinical malaria in prospective cohort studies carried out among African populations [13, 14]. Yet in another cohort study, the Hp 2–2 phenotype was associated with a higher susceptibility to P. falciparum infection among the Dogon, but not the Fulani, ethnic tribe of Mali [15]. In other studies where increased risk of developing P. falciparum symptomatic malaria among children carrying the Hp 2–2 genotype was reported [16], no associations between the Hp 1 allele and malaria susceptibility was found [14, 16]. The frequency of the Hp 1 and Hp 2 genes varies considerably in different populations. The Hp 1 allele frequency ranges from as low as 0.07 in parts of India to over 0.7 in West Africa and South American populations [8]. Frequencies of the Hp 1 allele were found to be 0.52 among Hispanics, 0.55 in Blacks, 0.44 among Caucasians, 0.31 among Asians living in the American region and 0.56 in the African region [8]. In a study that examined the role of Hp polymorphisms in determining
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susceptibility to P. falciparum infection and severity of malaria among Ghanaian children, Hp1-1, Hp 2–1, and Hp 2–2 genotypes occurred in 32.4%, 54.1%, and 13.5% children, respectively [17]. Two studies carried out in malaria endemic Kenyan coast found the prevalence of Hp 1–1, Hp 2–1 and Hp 2–2 phenotypes of 45%, 41% and 14% [13] and 28.5%, 45.2% and 26.4% of the study children, respectively [18]. In Uganda, there are no studies that have documented the frequency of Hp genotype
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