{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:49:41Z","timestamp":1791089381636,"version":"4.1.0"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2010,6,16]],"date-time":"2010-06-16T00:00:00Z","timestamp":1276646400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0011141","type":"journal-article","created":{"date-parts":[[2010,6,16]],"date-time":"2010-06-16T21:12:39Z","timestamp":1276722759000},"page":"e11141","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":45,"title":["Transforming Growth Factor Beta 2 and Heme Oxygenase 1 Genes Are Risk Factors for the Cerebral Malaria Syndrome in Angolan Children"],"prefix":"10.1371","volume":"5","author":[{"given":"Maria Ros\u00e1rio","family":"Sambo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jesus","family":"Trovoada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Benchimol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vat\u00fasia","family":"Quinhentos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00edgia","family":"Gon\u00e7alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rute","family":"Velosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Isabel","family":"Marques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuno","family":"Sep\u00falveda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taane G.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Mustafa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oswald","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f3nio","family":"Coutinho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Penha-Gon\u00e7alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2010,6,16]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.pt.2004.09.006","article-title":"Clinical features and pathogenesis of severe malaria.","volume":"20","author":"CL Mackintosh","year":"2004","journal-title":"Trends Parasitol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.4269\/ajtmh.2007.77.1015","article-title":"Differences in presentation of severe malaria in urban and rural Gabon.","volume":"77","author":"S Issifou","year":"2007","journal-title":"Am J Trop Med Hyg"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0163-7258(98)00008-4","article-title":"Severe falciparum malaria in children: current understanding of pathophysiology and supportive treatment.","volume":"79","author":"CR Newton","year":"1998","journal-title":"Pharmacol Ther"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/S1474-4422(05)70247-7","article-title":"Pathogenesis, clinical features, and neurological outcome of cerebral malaria.","volume":"4","author":"R Idro","year":"2005","journal-title":"Lancet Neurol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"e340","DOI":"10.1371\/journal.pmed.0020340","article-title":"Heritability of malaria in Africa.","volume":"2","author":"MJ Mackinnon","year":"2005","journal-title":"PLoS Med"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1086\/301967","article-title":"Malaria in humans: Plasmodium falciparum blood infection levels are linked to chromosome 5q31\u2013q33.","volume":"63","author":"P Rihet","year":"1998","journal-title":"Am J Hum Genet"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1086\/430744","article-title":"Sickle cell trait and the risk of Plasmodium falciparum malaria and other childhood diseases.","volume":"192","author":"TN Williams","year":"2005","journal-title":"J Infect Dis"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s001090050253","article-title":"Glucose-6-phosphate dehydrogenase deficiency and malaria.","volume":"76","author":"C Ruwende","year":"1998","journal-title":"J Mol Med"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"e66","DOI":"10.1371\/journal.pmed.0040066","article-title":"X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria.","volume":"4(3)","author":"A Guindo","year":"2007","journal-title":"PLoS Med"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/376246a0","article-title":"Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria.","volume":"376","author":"C Ruwende","year":"1995","journal-title":"Nature"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1182\/blood-2005-01-0313","article-title":"Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya.","volume":"106","author":"TN Williams","year":"2005","journal-title":"Blood"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1182\/blood-2003-11-4090","article-title":"Alpha(+)-thalassemia protects African children from severe malaria.","volume":"104","author":"FP Mockenhaupt","year":"2004","journal-title":"Blood"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"e158","DOI":"10.1371\/journal.pmed.0030158","article-title":"The effect of alpha+-thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya.","volume":"3","author":"S Wambua","year":"2006","journal-title":"PLoS Med"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1086\/432519","article-title":"How malaria has affected the human genome and what human genetics can teach us about malaria.","volume":"77","author":"DP Kwiatkowski","year":"2005","journal-title":"Am J Hum Genet"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/35016636","article-title":"Malaria susceptibility and CD36 mutation.","volume":"405","author":"TJ Aitman","year":"2000","journal-title":"Nature"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1086\/340516","article-title":"IFNGR1 gene promoter polymorphisms and susceptibility to cerebral malaria.","volume":"185","author":"O Koch","year":"2002","journal-title":"J Infect Dis"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00439-002-0882-4","article-title":"Nucleotide and haplotypic diversity of the NOS2A promoter region and its relationship to cerebral malaria.","volume":"112","author":"D Burgner","year":"2003","journal-title":"Hum Genet"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.1365-2249.2004.02590.x","article-title":"Allelic polymorphisms in the repeat and promoter regions of the interleukin-4 gene and malaria severity in Ghanaian children.","volume":"138","author":"BA Gyan","year":"2004","journal-title":"Clin Exp Immunol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1258\/td.2006.006352","article-title":"The causes of death of hospitalized children in Angola.","volume":"38","author":"EA e Pinto","year":"2008","journal-title":"Trop Doct"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7883\/yoken.JJID.2005.268","article-title":"Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to cerebral malaria in Myanmar.","volume":"58","author":"M Takeda","year":"2005","journal-title":"Jpn J Infect Dis"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1475-2875-6-32","article-title":"Bone marrow chimeric mice reveal a dual role for CD36 in Plasmodium berghei ANKA infection.","volume":"6","author":"M Cunha-Rodrigues","year":"2007","journal-title":"Malar J"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/sj.mn.7800159","article-title":"Regulation of endothelial cell adhesion molecule expression in an experimental model of cerebral malaria.","volume":"9","author":"PR Bauer","year":"2002","journal-title":"Microcirculation"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"776","DOI":"10.4269\/ajtmh.1999.61.776","article-title":"Association of the ICAM-1Kilifi mutation with protection against severe malaria in Lambarene, Gabon.","volume":"61","author":"JF Kun","year":"1999","journal-title":"Am J Trop Med Hyg"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1093\/hmg\/6.8.1357","article-title":"A high frequency African coding polymorphism in the N-terminal domain of ICAM-1 predisposing to cerebral malaria in Kenya.","volume":"6","author":"D Fernandez-Reyes","year":"1997","journal-title":"Hum Mol Genet"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/S0035-9203(98)91026-4","article-title":"Absence of an association between intercellular adhesion molecule 1, complement receptor 1 and interleukin 1 receptor antagonist gene polymorphisms and severe malaria in a West African population.","volume":"92","author":"R Bellamy","year":"1998","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/gene.2008.38","article-title":"Variation in the ICAM1 gene is not associated with severe malaria phenotypes.","volume":"9","author":"AE Fry","year":"2008","journal-title":"Genes Immun"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1111\/j.1399-0039.2005.00388.x","article-title":"Genetic study of ICAM1 in clinical malaria in Senegal.","volume":"65","author":"R Ndiaye","year":"2005","journal-title":"Tissue Antigens"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/S0140-6736(00)04662-6","article-title":"A non-sense mutation in Cd36 gene is associated with protection from severe malaria.","volume":"357","author":"A Pain","year":"2001","journal-title":"Lancet"},{"key":"ref29","first-page":"29","article-title":"Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes.","volume":"29","author":"AE Fry","year":"2009","journal-title":"Hum Mol Genet"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"e128","DOI":"10.1371\/journal.pmed.0020128","article-title":"An immune basis for malaria protection by the sickle cell trait.","volume":"2","author":"TN Williams","year":"2005","journal-title":"PLoS Med"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/35016636","article-title":"Malaria susceptibility and CD36 mutation.","volume":"405","author":"TJ Aitman","year":"2000","journal-title":"Nature"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1086\/346091","article-title":"CD36 polymorphism is associated with protection from cerebral malaria.","volume":"72","author":"K Omi","year":"2003","journal-title":"Am J Hum Genet"},{"key":"ref33","first-page":"1","article-title":"Polymorphisms of CD36 in Thai malaria patients.","volume":"33","author":"K Omi","year":"2002","journal-title":"Southeast Asian J Trop Med Public Health"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.4049\/jimmunol.172.6.3553","article-title":"Heme oxygenase-1 modulates the expression of adhesion molecules associated with endothelial cell activation.","volume":"172","author":"MP Soares","year":"2004","journal-title":"J Immunol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"7840","DOI":"10.4049\/jimmunol.179.11.7840","article-title":"Heme oxygenase-1 inhibits the expression of adhesion molecules associated with endothelial cell activation via inhibition of NF-kappaB RelA phosphorylation at serine 276.","volume":"179","author":"MP Seldon","year":"2007","journal-title":"J Immunol"},{"key":"ref36","first-page":"114","article-title":"Absence of association between the allele coding methionine at position 29 in the N-terminal domain of ICAM-1 (ICAM-1(Kilifi)) and severe malaria in the northwest of Thailand.","volume":"54","author":"J Ohashi","year":"2001","journal-title":"Jpn J Infect Dis"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1111\/j.1365-3156.2005.01444.x","article-title":"Limited influence of haptoglobin genotypes on severe malaria in Ghanaian children.","volume":"10","author":"U Bienzle","year":"2005","journal-title":"Trop Med Int Health"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/sj.gene.6363962","article-title":"Interferon-alpha receptor-1 (IFNAR1) variants are associated with protection against cerebral malaria in the Gambia.","volume":"4","author":"C Aucan","year":"2003","journal-title":"Genes Immun"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S1286-4579(02)01541-1","article-title":"Cerebral malaria: the contribution of studies in animal models to our understanding of immunopathogenesis.","volume":"4","author":"JB de Souza","year":"2002","journal-title":"Microbes Infect"},{"key":"ref40","first-page":"103","article-title":"Experimental models of cerebral malaria.","volume":"297","author":"C Engwerda","year":"2005","journal-title":"Curr Top Microbiol Immunol"},{"key":"ref41","first-page":"8","article-title":"Cerebral malaria: human versus mouse studies.","volume":"2010","author":"MM Stevenson","journal-title":"Trends Parasitol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"9919","DOI":"10.1073\/pnas.152215199","article-title":"Identification of two cerebral malaria resistance loci using an inbred wild-derived mouse strain.","volume":"99","author":"S Bagot","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/S0169-4758(99)01562-8","article-title":"Maintaining the immunological balance in parasitic infections: a role for TGF-beta?","volume":"16","author":"FM Omer","year":"2000","journal-title":"Parasitol Today"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1084\/jem.188.1.39","article-title":"Transforming growth factor beta production is inversely correlated with severity of murine malaria infection.","volume":"188","author":"FM Omer","year":"1998","journal-title":"J Exp Med"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.immuni.2005.08.006","article-title":"Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection.","volume":"23","author":"M Walther","year":"2005","journal-title":"Immunity"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1086\/315493","article-title":"Differential cellular accumulation of transforming growth factor-beta1, -beta2, and -beta3 in brains of patients who died with cerebral malaria.","volume":"181","author":"MH Deininger","year":"2000","journal-title":"J Infect Dis"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nm1586","article-title":"Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria.","volume":"13","author":"A Pamplona","year":"2007","journal-title":"Nat Med"},{"key":"ref48","first-page":"24","article-title":"Genome-wide and fine-resolution association analysis of malaria in West Africa.","volume":"24","author":"M Jallow","year":"2009","journal-title":"Nat Genet"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/nature07632","article-title":"A global network for investigating the genomic epidemiology of malaria.","volume":"456","year":"2008","journal-title":"Nature"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"e4037","DOI":"10.1371\/journal.pone.0004037","article-title":"Is replication the gold standard for validating genome-wide association findings?","volume":"3","author":"YJ Liu","year":"2008","journal-title":"PLoS ONE"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/447655a","article-title":"Replicating genotype-phenotype associations.","volume":"447","author":"SJ Chanock","year":"2007","journal-title":"Nature"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/0035-9203(91)90015-Q","article-title":"Comparison of two simple methods for determining malaria parasite density.","volume":"85","author":"BM Greenwood","year":"1991","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"ref53","first-page":"263","article-title":"Detection and identification of the four malaria parasite species infecting humans by PCR amplification.","volume":"50","author":"G Snounou","year":"1996","journal-title":"Methods Mol Biol"},{"key":"ref54","author":"L Gonzalez Fau - Armengol Jr"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1093\/bioinformatics\/btl657","article-title":"snp.plotter: an R-based SNP\/haplotype association and linkage disequilibrium plotting package.","volume":"23","author":"A Luna","year":"2007","journal-title":"Bioinformatics"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1093\/bioinformatics\/18.12.1694","article-title":"GENECOUNTING: haplotype analysis with missing genotypes.","volume":"18","author":"JH Zhao","year":"2002","journal-title":"Bioinformatics"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1086\/338688","article-title":"Score tests for association between traits and haplotypes when linkage phase is ambiguous.","volume":"70","author":"DJ Schaid","year":"2002","journal-title":"Am J Hum Genet"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1086\/302577","article-title":"A generalization of the transmission\/disequilibrium test for uncertain-haplotype transmission.","volume":"65","author":"D Clayton","year":"1999","journal-title":"Am J Hum Genet"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses.","volume":"81","author":"S Purcell","year":"2007","journal-title":"Am J Hum Genet"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0011141","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T01:14:01Z","timestamp":1740186841000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0011141"}},"subtitle":[],"editor":[{"given":"Mauricio Martins","family":"Rodrigues","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2010,6,16]]},"references-count":59,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2010,6,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0011141","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6,16]]}}}