Genetic Evidence for the Aggravation of<i>Plasmodium falciparum</i>Malaria by Interleukin 4

Cabantous, Stéphanie; Poudiougou, Belco; Oumar, Aboubacar Alassane; Traore, Abdoualye; Barry, Abdoulaye; Vitte, Joana; Bongrand, Pierre; Marquet, Sandrine; Doumbo, Ogobara K.; Dessein, Alain

doi:10.1086/644600

Cited by 37 publications

(24 citation statements)

References 45 publications

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“…This is consistent with the association study performed in the additional population [12], although the genetic markers associated with parasitaemia in the additional population and those associated with parasitaemia in the initial population were different. This is also consistent with linkage analyses in mice [11] and genetic studies in humans showing an association of IL3, IL4, IL13, IRF1, and ARHGAP26 with parasitaemia, mild malaria or severe malaria [6,27-30]. …”

Section: Discussionsupporting

confidence: 87%

A genome scan for Plasmodium falciparum malaria identifies quantitative trait loci on chromosomes 5q31, 6p21.3, 17p12, and 19p13

Brisebarre

Kumulungui

Sawadogo

et al. 2014

Malar J

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BackgroundGenome-wide studies have mapped several loci controlling Plasmodium falciparum mild malaria and parasitaemia, only two of them being significant at the genome level. The objective of the present study was to identify malaria resistance loci in individuals living in Burkina Faso.MethodsA genome scan that involved 314 individuals belonging to 63 families was performed. Markers located within chromosomes 6p21.3 and 17p12 were genotyped in 247 additional individuals belonging to 55 families. The linkage and the association of markers with parasitaemia and mild malaria were assessed by using the maximum-likelihood binomial method extended to quantitative trait linkage and the quantitative trait disequilibrium test, respectively.ResultsMultipoint linkage analysis showed a significant linkage of mild malaria to chromosome 6p21.3 (LOD score 3.73, P = 1.7 10−5), a suggestive linkage of mild malaria to chromosome 19p13.12 (LOD score 2.50, P = 3.5 10−4), and a suggestive linkage of asymptomatic parasitaemia to chromosomes 6p21.3 (LOD score 2.36, P = 4.9 10−4) and 17p12 (LOD score 2.87, P = 1.4 10−4). Genome-wide family-based association analysis revealed a significant association between three chromosome 5q31 markers and asymptomatic parasitaemia, whereas there was no association with mild malaria. When taking into account 247 additional individuals, a significant linkage of asymptomatic parasitaemia to chromosome 17p12 (LOD score 3.6, P = 2 10−5) was detected.ConclusionA new genome-wide significant malaria locus on chromosome 17p12 and a new suggestive locus on chromosome 19p13.12 are reported. Moreover, there was evidence that confirmed the influence of chromosomes 5q31 and 6p21.3 as loci controlling mild malaria or asymptomatic parasitaemia.

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Section: Discussionsupporting

confidence: 87%

A genome scan for Plasmodium falciparum malaria identifies quantitative trait loci on chromosomes 5q31, 6p21.3, 17p12, and 19p13

Brisebarre

Kumulungui

Sawadogo

et al. 2014

Malar J

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“…Some studies suggested that RP2/RP2 genotype is associated with low expression of this cytokine [34]. However, another study showed the possible association between RP1 allele and higher expression of the IL-4 [35].…”

Section: Discussionmentioning

confidence: 99%

Possible Association of IL-4 VNTR Polymorphism with Susceptibility to Preeclampsia

Salimi

Mohammadoo‐Khorasani

Yaghmaei

et al. 2014

BioMed Research International

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Preeclampsia (PE) is a pregnancy-specific disorder that results in maternal mortality and morbidity. Growing evidence indicated that cytokines are involved in the pathogenesis of PE and interleukin-4 VNTR polymorphism could be implicated in altering the PE risk. The aim of this study was to evaluate the possible association between IL-4 VNTR polymorphism and susceptibility to PE in Iranian population for the first time. Genetic polymorphism was evaluated in 192 PE and 186 healthy control women by polymerase chain reaction method. We found that the VNTR polymorphism of IL-4 gene has significantly increased the risk of preeclampsia (RP2/RP1 versus RP1/RP1, OR, 2.8 [95% CI, 1.7 to 8.8]; P = 0.0001 and RP2/RP2 versus RP1/RP1; P = 0.002). The results showed that carriage of IL-4 VNTR RP2 allele has positive association with preeclampsia susceptibility.

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“…Malian children with CM were recruited as described previously (14)(15)(16)(17). The children with CM were hospitalized between 1999 and 2003 in the pediatric department of the Gabriel Toure Hospital in Bamako (Mali).…”

Section: Methodsmentioning

confidence: 99%

The IL17F and IL17RA Genetic Variants Increase Risk of Cerebral Malaria in Two African Populations

et al. 2016

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jCerebral malaria (CM) is a neurological complication of infection with Plasmodium falciparum that is partly caused by cytokine-mediated inflammation. It is not known whether interleukin-17 (IL-17) cytokines, which regulate inflammation, control the development of CM. To evaluate the involvement of IL-17 cytokines in CM, we analyzed 46 common polymorphisms in IL17A, IL17F, and IL17RA (which encodes the common receptor chain of the members of the IL-17 family) in two independent African populations. A case-control study involving 115 Nigerian children with CM and 160 controls from the community (CC) showed that IL17F reference single nucleotide polymorphism (SNP) 6913472 (rs6913472) (P ‫؍‬ 0.004; odds ratio [OR] ‫؍‬ 3.12), IL17F rs4715291 (P ‫؍‬ 0.004; OR ‫؍‬ 2.82), IL17RA rs12159217 (P ‫؍‬ 0.01; OR ‫؍‬ 2.27), and IL17RA rs41396547 (P ‫؍‬ 0.026; OR ‫؍‬ 3.15) were independently associated with CM. A replication study was performed in 240 nuclear Malian family trios (two parents with one CM child). We replicated the association for 3 SNPs, IL17F rs6913472 (P ‫؍‬ 0.03; OR ‫؍‬ 1.39), IL17RA rs12159217 (P ‫؍‬ 0.01; OR ‫؍‬ 1.52), and IL17RA rs41396547 (P ‫؍‬ 0.04; OR ‫؍‬ 3.50). We also found that one additional SNP, IL17RA rs41433045, in linkage disequilibrium (LD) with rs41396547, was associated with CM in both Nigeria and Mali (P ‫؍‬ 0.002; OR ‫؍‬ 4.12 in the combined sample). We excluded the possibility that SNPs outside IL17F and IL17RA, in strong LD with the associated SNPs, could account for the observed associations. Furthermore, the results of a functional study indicated that the aggravating GA genotype of IL17F rs6913472 was associated with lower IL-17F concentrations. Our findings show for the first time that IL17F and IL17RA polymorphisms modulate susceptibility to CM and provide evidence that IL-17F protects against CM. C erebral malaria (CM) is one of the most severe complications of infection with Plasmodium falciparum and occurs predominantly in young children under 5 years of age and in "nonimmune" adults. The clinical characteristics of CM are an unarousable coma lasting for at least 1 h, with or without generalized convulsions, and asexual P. falciparum parasitemia with normal cerebrospinal fluid and no other cause of encephalopathy. This reversible encephalopathy is characterized by the sequestration of infected red blood cells (IRBC) in the capillaries of the brain together with the accumulation of leukocytes, platelets, and uninfected red blood cells (URBC) causing mechanical obstruction of microvessels and excessive activation of immune cells. Other pathological consequences are brain edema, alterations of the integrity of the blood-brain barrier (BBB), microhemorrhages, and tissue necrosis (1). However, despite the large number of studies that have investigated CM, the orchestration of the pathogenic mechanisms leading to CM is not well understood.Proinflammatory cytokines are thought to contribute to brain pathology in CM. Interleukin-17A (IL-17A) and IL-17F, the best-studied members of the IL-...

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Genetic Evidence for the Aggravation ofPlasmodium falciparumMalaria by Interleukin 4

Cited by 37 publications

References 45 publications

A genome scan for Plasmodium falciparum malaria identifies quantitative trait loci on chromosomes 5q31, 6p21.3, 17p12, and 19p13

A genome scan for Plasmodium falciparum malaria identifies quantitative trait loci on chromosomes 5q31, 6p21.3, 17p12, and 19p13

Possible Association of IL-4 VNTR Polymorphism with Susceptibility to Preeclampsia

The IL17F and IL17RA Genetic Variants Increase Risk of Cerebral Malaria in Two African Populations

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