Genetics of susceptibility to malaria related phenotypes

Carpenter, Danielle; Rooth, Ingegerd; Färnert, Anna; Abushama, Hind Mohamed; Quinnell, Rupert J.; Shaw, Marie‐Anne

doi:10.1016/j.meegid.2008.10.008

Cited by 14 publications

(31 citation statements)

References 36 publications

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“…Results indicate that, in children, density of Plasmodium parasitaemia in this Ugandan community is controlled to some degree by additive genetic factors, which account for approximately one-quarter of the phenotypic variation. This is remarkably consistent with previous quantitative genetic studies conducted in several epidemiological settings 8,9,28,29. In contrast, there was no evidence for genetic control of parasitaemia in adults.…”

Section: Discussionsupporting

confidence: 92%

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Heritability of Plasmodium Parasite Density in a Rural Ugandan Community

Pullan

Bukirwa²,

Snow³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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Many factors influence variation in Plasmodium infection levels, including parasite/host genetics, immunity, and exposure. Here, we examine the roles of host genetics and exposure in determining parasite density, and test whether effects differ with age. Data for 1,711 residents of an eastern Ugandan community were used in pedigree-based variance component analysis. Heritability of parasite density was 13% (P < 0.001) but was not significant after controlling for shared household. Allowing variance components to vary between children (< 16 years) and adults (≥ 16 years) revealed striking age differences; 26% of variation could be explained by additively acting genes in children (P < 0.001), but there was no genetic involvement in adults. Domestic environment did not explain variation in children and explained 5% in adults (P = 0.09). Genetic effects are an important determinant of parasite density in children in this population, consistent with previous quantitative genetic studies of Plasmodium parasitaemia, although differences in environmental exposure play a lesser role.

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Section: Discussionsupporting

confidence: 92%

“…However, in terms of total genetic contribution, the only studies to report heritability for asymptomatic parasite densities have been unable to account for shared household effects. They did, however, show significant heritability of between 10% and 33% in Tanzanian and Senegalese populations 28,29…”

Section: Introductionmentioning

confidence: 83%

Heritability of Plasmodium Parasite Density in a Rural Ugandan Community

Pullan

Bukirwa²,

Snow³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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“…The IL10-1082 polymorphism also had little effect on IL-10 levels in culture cells stimulated by M. tuberculosis antigens [27]. This study shows that neither polymorphism nor any combination of genotypes was associated with differences in the elimination of the parasite, as described for P. falciparum patients [56]. Taken together, our results suggest that a negative regulation mediated by IL-10 and the polymorphism in IFN-γ gene (IFNG+874) provides a control mechanism in P. vivax malaria.…”

Section: Discussionmentioning

confidence: 84%

Increased interleukin-10 and interferon-γ levels in Plasmodium vivax malaria suggest a reciprocal regulation which is not altered by IL-10 gene promoter polymorphism

Medina

Costa

Oliveira

et al. 2011

Malar J

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BackgroundIn human malaria, the naturally-acquired immune response can result in either the elimination of the parasite or a persistent response mediated by cytokines that leads to immunopathology. The cytokines are responsible for all the symptoms, pathological alterations and the outcome of the infection depends on the reciprocal regulation of the pro and anti-inflammatory cytokines. IL-10 and IFN-gamma are able to mediate this process and their production can be affected by single nucleotide polymorphisms (SNPs) on gene of these cytokines. In this study, the relationship between cytokine IL-10/IFN-gamma levels, parasitaemia, and their gene polymorphisms was examined and the participation of pro-inflammatory and regulatory balance during a natural immune response in Plasmodium vivax-infected individuals was observed.MethodsThe serum levels of the cytokines IL-4, IL-12, IFN-gamma and IL-10 from 132 patients were evaluated by indirect enzyme-linked immunosorbent assays (ELISA). The polymorphism at position +874 of the IFN-gamma gene was identified by allele-specific polymerase chain reaction (ASO-PCR) method, and the polymorphism at position -1082 of the IL-10 gene was analysed by PCR-RFLP (PCR-Restriction Fragment Length Polymorphism).ResultsThe levels of a pro- (IFN-gamma) and an anti-inflammatory cytokine (IL-10) were significantly higher in P. vivax-infected individuals as compared to healthy controls. The IFN-gamma levels in primoinfected patients were significantly higher than in patients who had suffered only one and more than one previous episode. The mutant alleles of both IFN-gamma and IL-10 genes were more frequent than the wild allele. In the case of the IFNG+874 polymorphism (IFN-gamma) the frequencies of the mutant (A) and wild (T) alleles were 70.13% and 29.87%, respectively. Similar frequencies were recorded in IL-10-1082, with the mutant (A) allele returning a frequency of 70.78%, and the wild (G) allele a frequency of 29.22%. The frequencies of the alleles associated with reduced production of both IFN-gamma and IL-10 were high, but this effect was only observed in the production of IFN-gamma.ConclusionsThis study has shown evidence of reciprocal regulation of the levels of IL-10 and IFN-gamma cytokines in P. vivax malaria, which is not altered by the presence of polymorphism in the IL-10 gene.

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“…For example, hundreds of millions of children in Africa are infected by and harbor P falciparum malaria and EBV, but only relatively few develop BL [14]. The biological characteristics of malaria, EBV, or host genetics that influence the risk of BL in settings of high P. falciparum malaria endemicity are incompletely understood [8].…”

Section: Introductionmentioning

confidence: 99%

“…In addition we have little understanding of the relationship between biological markers of malaria, such as crude parasite prevalence, parasite load, mixed genotype infections and/or humoral immunity, and risk of BL. Also unexplained is why the risk of BL peaks between 5–9 years[16] in people who reside in malaria endemic areas, given that peak intensity of exposure is between 0–2 years and people continue to be exposed to sub-clinical and clinical malaria for life [14]. We would expect the biological effects of malaria to begin earlier and persist for life in holoendemic malaria areas.…”

Section: Introductionmentioning

confidence: 99%

Incidence and trends in Burkitt lymphoma in northern Tanzania from 2000 to 2009

Aka

Kawira²,

Masalu

et al. 2012

Pediatric Blood & Cancer

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Introduction Burkitt lymphoma (BL) is endemic in parts of Tanzania, but there is scant country or region level data about burden and trends of BL in Tanzania over the past three decades. Here, we update baseline epidemiology of BL in northern Tanzania using recent data. Procedure Data for childhood BL diagnosed at six hospitals in Mara and Mwanza regions in northern Tanzania during 2000 – 2009 were compiled. Age, sex, and regional patterns were analyzed. Crude incidence rates of BL were calculated by sex, anatomic site, geographical region, and calendar year. Results Among 944 cases, 549 (58%) were male (male/female case ratio 1.4:1). Among those with known anatomic site (92%), facial only tumors represented a large proportion of tumors in boys than girls (50% versus 36%, P<0.002). Tumors occurred at a younger mean age in boys than girls (6.8 versus 7.6 years, P<0.01). Crude BL incidence was 4.2 per 100,000, but varied by region (3.0 in Mwanza versus 6.8 in Mara, P=0.01), by district (from 1.4 to 22), by gender (5.0 in boys versus 4.0 in girls) and by age group (2.0 in 0–4, 7.8 in 5–9, and 3.1 in 10–15 years). BL incidence peaked in 2001 and decreased gradually thereafter. Conclusions Our results indicate that male sex, young age, and geographical characteristics are risk factors for BL in Tanzania. BL incidence declined with calendar year, but the significance of this finding is uncertain. Well-designed epidemiological studies of BL in Tanzania may shed light on environmental characteristics underlying these patterns.

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Genetics of susceptibility to malaria related phenotypes

Cited by 14 publications

References 36 publications

Heritability of Plasmodium Parasite Density in a Rural Ugandan Community

Heritability of Plasmodium Parasite Density in a Rural Ugandan Community

Increased interleukin-10 and interferon-γ levels in Plasmodium vivax malaria suggest a reciprocal regulation which is not altered by IL-10 gene promoter polymorphism

Incidence and trends in Burkitt lymphoma in northern Tanzania from 2000 to 2009

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