Association of adhesion molecule PECAM-1/CD31 polymorphism with susceptibility to cerebral malaria in Thais

Kikuchi, Mihoko; Looareesuwan, S; Ubalee, Ratawan; Tasanor, Oumaporn; Suzuki, Fumiharu; Wattanagoon, Yupaporn; Na‐Bangchang, Kesara; Kimura, Akinori; Aikawa, Masamichi; Hirayama, Kenji

doi:10.1016/s1383-5769(01)00082-4

Cited by 30 publications

(20 citation statements)

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“…Family-based studies avoid biases due to population stratification. This refers to a situation in which the study population includes two subpopulations genetically different; in this case, the two subpopulations differ in allele frequencies at a number of genetic markers located within different chromosomal regions (18,25,69,75,76,82,95,96,105,108,124,125,130,165,180). Since these differences can be due to different population histories, family-based studies should be useful to clarify this point.…”

Section: Current Lessons From Human Genetic Studies Of Resistance To mentioning

confidence: 99%

Host susceptibility to malaria in human and mice: compatible approaches to identify potential resistant genes

Hernandez-Valladares¹,

Rihet

Iraqi

2014

Physiological Genomics

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Hernandez-Valladares M, Rihet P, Iraqi FA. Host susceptibility to malaria in human and mice: compatible approaches to identify potential resistant genes. Physiol Genomics 46: 1-16, 2014. First published October 29, 2013 doi:10.1152/physiolgenomics.00044.2013.-There is growing evidence for human genetic factors controlling the outcome of malaria infection, while molecular basis of this genetic control is still poorly understood. Case-control and family-based studies have been carried out to identify genes underlying host susceptibility to malarial infection. Parasitemia and mild malaria have been genetically linked to human chromosomes 5q31-q33 and 6p21.3, and several immune genes located within those regions have been associated with malaria-related phenotypes. Association and linkage studies of resistance to malaria are not easy to carry out in human populations, because of the difficulty in surveying a significant number of families. Murine models have proven to be an excellent genetic tool for studying host response to malaria; their use allowed mapping 14 resistance loci, eight of them controlling parasitic levels and six controlling cerebral malaria. Once quantitative trait loci or genes have been identified, the human ortholog may then be identified. Comparative mapping studies showed that a couple of human and mouse might share similar genetically controlled mechanisms of resistance. In this way, char8, which controls parasitemia, was mapped on chromosome 11; char8 corresponds to human chromosome 5q31-q33 and contains immune genes, such as Il3, Il4, Il5, Il12b, Il13, Irf1, and Csf2. Nevertheless, part of the genetic factors controlling malaria traits might differ in both hosts because of specific hostpathogen interactions. Finally, novel genetic tools including animal models were recently developed and will offer new opportunities for identifying genetic factors underlying host phenotypic response to malaria, which will help in better therapeutic strategies including vaccine and drug development. malaria; genetic resistance; human; mouse model; QT mapping PLASMODIUM FALCIPARUM MALARIA remains a major cause of morbidity and mortality in many developing countries. According to the World Health Organization (WHO), the number of cases in 2012 reached 219 million [95% confidence interval (CI) 154 -289 million], among which Ͼ660,000 (95% CI 490,000 -836,000) were fatal (62, 181a). Drug-resistant parasite strains are spreading rapidly across the world, and, despite substantial efforts and encouraging results from recent trials, a fully protective malaria vaccine remains a distant prospect (154). Vaccine development faces major difficulties partly due to the genetic control of immunity to the parasite (155,156,163,176) and/or to the parasitic antigenic variation (146).The outcome of human malaria infection is thought to depend on both parasite and host genetic factors. P. falciparum genotypes have been associated with differences in disease outcome (41) and may be subject to selective pressure (34,55). The influ...

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Section: Current Lessons From Human Genetic Studies Of Resistance To mentioning

confidence: 99%

Host susceptibility to malaria in human and mice: compatible approaches to identify potential resistant genes

Hernandez-Valladares¹,

Rihet

Iraqi

2014

Physiological Genomics

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“…Analisis polimorfisme PECAM-1 pada pasien malaria menunjukkan bahwa frekuensi satu genotipe sangat beresiko menjadi malaria serebral (28). Reseptor sel endotel lainnya pada skala kecil selama infeksi seperti alfa (v) beta3 atau integrin terlibat dengan beberapa proses adherensi patologis dan fisiologis.…”

Section: Mekanisme Molekuler Cytoadherenceunclassified

Intervensi Cytoadherence Sebagai Peluang Untuk Pencegahan Dan Terapi Malaria Berat

Simamora

Sumitro

Fitri

2013

JKB

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In malarial infection, erythrocytes infected wih Plasmodium falciparum bind to endothelial vascular (endothelial cytoadherence). This binding is implicated in the forming of sequestre and rosette that affects the vascular circulation, and thus injures the capillary wall. This mechanism is important in pathogenesis of malarial due to dysfunction of several organs. There are several receptors of cytoadherence in human e.g Thrombospondine (TSP), CD-36, ICAM-1, and ELAM-1 as well as specific ligands of the parasite e.g Plasmodium falciparum Erythrocyte Membrane Protein-1 (PfEMP-1), 220 kDa protein of Pf60, Pf332, sequestrin, Pfaldhesin and STEVOR. PfEMP-1 has been revealed as a molecule that is responsible for pathogenesis of severe malaria. This protein can pass parasitophorous vacoular membrane (PVM) of the parasite by attaching its molecule to carry Protein Export Elemen (PEXEL) and than go to the surface of erythrocytes in combination with specific helper protein in maeurer cleft. The intervention on cytoadherence process through blocking of specific ligand directly or blocking the translocation of this ligand to the surface of erythrocytes might be important in regulating the outcome of malarial infection.Key words : Cytoadherence, severe malaria, intervention, adhesion molecule. PENDAHULUANSiklus eritrositik dari Plasmodium falciparum yang menyerang manusia memiliki mekanisme yang berbeda bila dibandingkan dengan spesies Plasmodium lain. Trophozoite dan schizont dewasa akan hilang dari sirkulasi perifer akibat adanya adhesi eritrosit yang terinfeksi pada sel endotel kapiler pembuluh organ dalam. Adhesi eritrosit menghasilkan maturasi yang lebih baik dalam lingkungan mikroaerofilik venous serta akan membuat parasit ini terhindar dari proses pembersihan dari limpa. Dalam tekanan gas yang rendah parasit akan lebih cepat berdiferensiasi dan eritrosit bentuk aseksual (trophozoite dan schizont) juga akan lebih cepat menjadi matur (1).Protein adhesi yang terletak pada permukaan eritrosit yang terinfeksi disebut knob. Knob ini akan memudahkan terjadinya adhesi pada sel endotel dan eritrosit lainnya.. Adhesi pada endotel atau cytoadherence, berperan penting dalam patogenesis penyakit, karena dapat menyebabkan oklusi pada pembuluh darah kecil serta dapat menyebabkan gagal fungsi pada beberapa organ. Protein membran eritrosit 1 dari P. falciparum (PfEMP-1) merupakan ligand adhesif utama dari eritrosit yang terinfeksi (1).Cytoadherence dapat mengakibatkan kerusakan pada dinding pembuluh darah kapiler serta dapat menghambat aliran darah ke pembuluh darah kapiler karena terbentuknya sequester dan rosette. Proses tersebut menyebabkan terjadinya edema dan hipoksia karena adanya kebocoran kapiler dan berkurangnya aliran darah. (2). Gambar 1. Eritrosit dalam Keadaan Terinfeksi ParasitP. falciparum (1).

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“…Similarly, Song et al (2003) found a significant increase in the frequencies of V 98 and N 536 polymorphisms in patients presenting with early onset of coronary artery disease (CAD), while two other studies (Fang et al, 2005;Wei et al, 2004) found only V 98 associated with CAD. Finally, PECAM-1 serves as an endothelial cell receptor for certain strains of Plasmodium falciparum-infected erythrocytes, and there are two reports regarding susceptibility of individuals carrying the Leu 98 polymorphism to malarial infection: one showing an association (Kikuchi et al, 2001) and one not showing such a connection (Casals-Pascual et al, 2001). It is possible that re-genotyping these populations for PECAM-1 alleles, including the newly described 3′UTR polymorphism at nucleotide 2479 (this manuscript), rather than for individual SNPs, might help resolve the seemingly disparate results obtained in each of these studies.…”

Section: Disease Associations With Pecam-1 Allelic Isoformsmentioning

confidence: 99%

“…While the effects of these polymorphisms on PECAM-1-mediated adhesion or signaling have not yet been determined, mismatches at PECAM-1 amino acid residues 98, 536, or 643 have often (Balduini et al, 1999;Behar et al, 1996;Cavanagh et al, 2005;Grumet et al, 2001;Maruya et al, 1998), though not universally (Nichols et al, 1996), been associated with an increased incidence of acute graft-versushost disease (GVHD), and these and other PECAM-1 polymorphisms have been linked with early onset of atherosclerosis (Elrayess et al, 2003), increased risk of cardiovascular disease (Elrayess et al, 2004;Fang et al, 2005;Listi et al, 2004;Sasaoka et al, 2001;Song et al, 2003;Wei et al, 2004), and susceptibility to malarial infection (Kikuchi et al, 2001), though the latter is also controversial (Casals-Pascual et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

The alleles of PECAM-1

Novinska

Pietz

Ellis

et al. 2006

Gene

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Previous studies have reported the existence of eleven different single nucleotide polymorphisms (SNPs) within human PECAM-1 mRNA, several of which have recently been associated with disease. Though SNPs in the PECAM-1 gene have been known for some time, the genetic background on which they exist, and their association into distinct allelic isoforms has not yet been established. To identify the major allelic isoforms of PECAM-1, we determined the nucleotide sequence of individual full-length cloned cDNAs derived from anonymous, unrelated volunteer individuals. Initial sequence analysis of 34 alleles from 17 individuals confirmed the presence of two distinct human PECAM-1 alleles (L(98)S(536)R(643) and V(98)N(536)G(643)) within the human population. Each of these were found, upon more detailed analysis, to be superimposed on a previously unreported a2479g nucleotide polymorphism within the 3' untranslated region (3'UTR) that occurred on both allelic isoforms - yielding a total of four major alleles. Multiplex Luminex bead analysis of an additional 259 individuals allowed identification of 117 individuals homozygous for either the L(98)S(536) or V(98)N(536) allele, and sequence analysis around the R643G and a2479g polymorphic sites permitted accurate determination of significant differences in the gene frequencies of LSRa, LSRg, VNGa, and VNGg among Caucasian individuals. Identification of these PECAM-1 allelic isoforms should facilitate future detailed examination of PECAM-1-related disease associations, and may help resolve previously disparate results.

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Association of adhesion molecule PECAM-1/CD31 polymorphism with susceptibility to cerebral malaria in Thais

Cited by 30 publications

References 17 publications

Host susceptibility to malaria in human and mice: compatible approaches to identify potential resistant genes

Host susceptibility to malaria in human and mice: compatible approaches to identify potential resistant genes

Intervensi Cytoadherence Sebagai Peluang Untuk Pencegahan Dan Terapi Malaria Berat

The alleles of PECAM-1

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