A high frequency African coding polymorphism in the N-terminal domain of ICAM-1 predisposing to cerebral malaria in Kenya

Fernández-Reyes, Delmiro; Craig, Alister G.; Kyes, Sue; Peshu, Norbert; Snow, Robert W.; Berendt, Anthony R.; Marsh, Kevin; Newbold, Chris

doi:10.1093/hmg/6.8.1357

Cited by 174 publications

(125 citation statements)

References 20 publications

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“…Moreover, multiple distinct episodes of selection may have operated on the TNF and ICAM1 genes, in view of their central importance in interacting with pathogens and in other noninfectious diseases. The ICAM1 Kili f t variant has been found to predispose individuals in Kenya to cerebral malaria (Fernandez-Reyes et al 1997). Although this variant was found in several populations in our study, its frequency is much lower than in Kenya.…”

Section: Resultscontrasting

confidence: 66%

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Patterns of nucleotide sequence variation in ICAM1 and TNF genes in twelve ethnic groups of India: roles of demographic history and natural selection

Sengupta

Farheen

Mukherjee

et al. 2007

J Genet

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We have studied DNA sequence variation in and around the genes ICAM1 and TNF, which play functional and correlated roles in inflammatory processes and immune cell responses, in 12 diverse ethnic groups of India, with a view to investigating the relative roles of demographic history and natural selection in shaping the observed patterns of variation. The total numbers of single nucleotide polymorphisms (SNPs) detected at the ICAM1 and TNF loci were 29 and 12, respectively. Haplotype and allele frequencies differed significantly across populations. The site frequency spectra at these loci were significantly different from those expected under neutrality, and showed an excess of intermediate-frequency variants consistent with balancing selection. However, as expected under balancing selection, there was no significant reduction of F S T values compared to neutral autosomal loci. Mismatch distributions were consistent with population expansion for both loci. On the other hand, the phylogenetic network among haplotypes for the TNF locus was similar to expectations under population expansion, while that for the ICAM1 was as expected under balancing selection. Nucleotide diversity at the ICAM1 locus was an order of magnitude lower in the promoter region, compared to the introns or exons, but no such difference was noted for the TNF gene. Thus, we conclude that the pattern of nucleotide variation in these genes has been modulated by both demographic history and selection. This is not surprising in view of the known allelic associations of several polymorphisms in these genes with various diseases, both infectious and noninfectious.[Sengupta S., Farheen S., Mukherjee N. and Majumder P. P. 2007 Patterns of nucleotide sequence variation in ICAM1 and TNF genes in twelve ethnic groups of India: roles of demographic history and natural selection. J. Genet. 86,[225][226][227][228][229][230][231][232][233][234][235][236][237][238][239]

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Section: Resultscontrasting

confidence: 66%

“…Both ICAM1 and TNF, appear to play an important roles in malarial susceptibility (Hill 1992;Fernandez-Reyes et al 1997;McGuire et al 1999). The pathogenecity of Plasmodium falciparum has been *For correspondence.…”

Section: Introductionmentioning

confidence: 99%

Patterns of nucleotide sequence variation in ICAM1 and TNF genes in twelve ethnic groups of India: roles of demographic history and natural selection

Sengupta

Farheen

Mukherjee

et al. 2007

J Genet

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“…Furthermore, a human ICAM-1 polymorphism that occurs at high frequency in Africa (57) and reduces the ability of P. falciparum to bind to ICAM-1 (53, 58) does not protect against CM or severe malaria (59). In the work shown here, although ICAM-1 is expressed on the surface of HBEC-5i, it is not the receptor used by the HBEC-selected parasites because (i) in spot-binding assays HBEC-selected parasites did not show increased binding to recombinant ICAM-1 compared with -unselected parasites (SI Appendix, Fig.…”

Section: Discussionmentioning

confidence: 99%

A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells

Claessens

Adams

Ghumra

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

197

230

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Cerebral malaria is the most deadly manifestation of infection with Plasmodium falciparum. The pathology of cerebral malaria is characterized by the accumulation of infected erythrocytes (IEs) in the microvasculature of the brain caused by parasite adhesins on the surface of IEs binding to human receptors on microvascular endothelial cells. The parasite and host molecules involved in this interaction are unknown. We selected three P. falciparum strains (HB3, 3D7, and IT/FCR3) for binding to a human brain endothelial cell line (HBEC-5i). The whole transcriptome of isogenic pairs of selected and unselected parasites was analyzed using a variant surface antigen-supplemented microarray chip. After selection, the most highly and consistently up-regulated genes were a subset of group A-like var genes (HB3var3, 3D7_PFD0020c, ITvar7, and ITvar19) that showed 11-to >100-fold increased transcription levels. These var genes encode P. falciparum erythrocyte membrane protein (PfEMP)1 variants with distinct N-terminal domain types (domain cassette 8 or domain cassette 13). Antibodies to HB3var3 and PFD0020c recognized the surface of live IEs and blocked binding to HBEC-5i, thereby confirming the adhesive function of these variants. The clinical in vivo relevance of the HBEC-selected parasites was supported by significantly higher surface recognition of HBEC-selected parasites compared with unselected parasites by antibodies from young African children suffering cerebral malaria (Mann-Whitney test, P = 0.029) but not by antibodies from controls with uncomplicated malaria (Mann-Whitney test, P = 0.58). This work describes a binding phenotype for virulence-associated group A P. falciparum erythrocyte membrane protein 1 variants and identifies targets for interventions to treat or prevent cerebral malaria.adherence | pathogenesis | sequestration

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“…Moreover, although associations have been found between the incidence of disease and host genetic polymorphisms in cell receptors known to bind malaria parasites through PfEMP-1, these have been in the unexpected direction, i.e. the more common variants in malaria-endemic areas are associated with severe malaria (Fernandez-Reyes et al 1997;Aitman et al 2000). The relationship between PfEMP-1, cytoadherence-related disease and strain-specific immunity is clearly complex.…”

Section: (B) Antigenic Variationmentioning

confidence: 99%

Virulence in malaria: an evolutionary viewpoint

Mackinnon

Read

2004

Phil. Trans. R. Soc. Lond. B

227

205

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Malaria parasites cause much morbidity and mortality to their human hosts. From our evolutionary perspective, this is because virulence is positively associated with parasite transmission rate. Natural selection therefore drives virulence upwards, but only to the point where the cost to transmission caused by host death begins to outweigh the transmission benefits. In this review, we summarize data from the laboratory rodent malaria model, Plasmodium chabaudi, and field data on the human malaria parasite, P. falciparum, in relation to this virulence trade-off hypothesis. The data from both species show strong positive correlations between asexual multiplication, transmission rate, infection length, morbidity and mortality, and therefore support the underlying assumptions of the hypothesis. Moreover, the P. falciparum data show that expected total lifetime transmission of the parasite is maximized in young children in whom the fitness cost of host mortality balances the fitness benefits of higher transmission rates and slower clearance rates, thus exhibiting the hypothesized virulence trade-off. This evolutionary explanation of virulence appears to accord well with the clinical and molecular explanations of pathogenesis that involve cytoadherence, red cell invasion and immune evasion, although direct evidence of the fitness advantages of these mechanisms is scarce. One implication of this evolutionary view of virulence is that parasite populations are expected to evolve new levels of virulence in response to medical interventions such as vaccines and drugs.

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A high frequency African coding polymorphism in the N-terminal domain of ICAM-1 predisposing to cerebral malaria in Kenya

Cited by 174 publications

References 20 publications

Patterns of nucleotide sequence variation in ICAM1 and TNF genes in twelve ethnic groups of India: roles of demographic history and natural selection

Patterns of nucleotide sequence variation in ICAM1 and TNF genes in twelve ethnic groups of India: roles of demographic history and natural selection

A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells

Virulence in malaria: an evolutionary viewpoint

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