{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:56:51Z","timestamp":1789617411167,"version":"build-2803163510"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T00:00:00Z","timestamp":1485820800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T00:00:00Z","timestamp":1485820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cerebral malaria (CM) is a severe complication of<jats:italic>Plasmodium falciparum<\/jats:italic>infection. This encephalopathy is characterized by coma and is thought to result from mechanical microvessel obstruction and an excessive activation of immune cells leading to pathological inflammation and blood-brain barrier alterations. IL-22 contributes to both chronic inflammatory and infectious diseases, and may have protective or pathogenic effects, depending on the tissue and disease state. We evaluated whether polymorphisms (<jats:italic>n<\/jats:italic>\u2009=\u200946) of<jats:italic>IL22<\/jats:italic>and<jats:italic>IL22RA2<\/jats:italic>were associated with CM in children from Nigeria and Mali. Two SNPs of<jats:italic>IL22<\/jats:italic>, rs1012356 (<jats:italic>P<\/jats:italic>\u2009=\u20090.016, OR\u2009=\u20092.12) and rs2227476 (<jats:italic>P<\/jats:italic>\u2009=\u20090.007, OR\u2009=\u20092.08) were independently associated with CM in a sample of 115 Nigerian children with CM and 160 controls. The association with rs2227476 (<jats:italic>P<\/jats:italic>\u2009=\u20090.01) was replicated in 240 nuclear families with one affected child from Mali. SNP rs2227473, in linkage disequilibrium with rs2227476, was also associated with CM in the combined cohort for these two populations, (<jats:italic>P<\/jats:italic>\u2009=\u20090.004, OR\u2009=\u20091.55). SNP rs2227473 is located within a putative binding site for the aryl hydrocarbon receptor, a master regulator of IL-22 production. Individuals carrying the aggravating T allele of rs2227473 produced significantly more IL-22 than those without this allele. Overall, these findings suggest that IL-22 is involved in the pathogenesis of CM.<\/jats:p>","DOI":"10.1038\/srep41636","type":"journal-article","created":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T11:13:25Z","timestamp":1485861205000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A Functional IL22 Polymorphism (rs2227473) Is Associated with Predisposition to Childhood Cerebral Malaria"],"prefix":"10.1038","volume":"7","author":[{"given":"Sandrine","family":"Marquet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ianina","family":"Conte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belco","family":"Poudiougou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Argiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9lia","family":"Dessein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charl\u00e8ne","family":"Couturier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Burt\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aboubacar A.","family":"Oumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biobele J.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdoualye","family":"Traore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel K.","family":"Afolabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdoulaye","family":"Barry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Omokhodion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuraola A.","family":"Shokunbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olugbemiro","family":"Sodeinde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ogobara","family":"Doumbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delmiro","family":"Fernandez-Reyes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain J.","family":"Dessein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,31]]},"reference":[{"key":"BFsrep41636_CR1","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1111\/j.1365-3156.2004.01366.x","volume":"10","author":"EN Gitau","year":"2005","unstructured":"Gitau, E. N. Newton CR: Review Article. Blood-brain barrier in falciparum malaria. Trop Med Int Health. 10, 285\u2013292 (2005).","journal-title":"Trop Med Int Health"},{"key":"BFsrep41636_CR2","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1160\/TH05-05-0354","volume":"94","author":"P Pino","year":"2005","unstructured":"Pino, P., Taoufiq, Z., Nitcheu, J., Vouldoukis, I. & Mazier, D. Blood-brain barrier breakdown during cerebral malaria: suicide or murder? Thromb Haemost. 94, 336\u2013340 (2005).","journal-title":"Thromb Haemost"},{"key":"BFsrep41636_CR3","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.ijpara.2006.02.004","volume":"36","author":"IM Medana","year":"2006","unstructured":"Medana, I. M. Turner GD: Human cerebral malaria and the blood-brain barrier. Int J Parasitol. 36, 555\u2013568 (2006).","journal-title":"Int J Parasitol"},{"key":"BFsrep41636_CR4","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/mi.2008.26","volume":"1","author":"W Ouyang","year":"2008","unstructured":"Ouyang, W. & Valdez, P. IL-22 in mucosal immunity. Mucosal Immunol. 1, 335\u2013338 (2008).","journal-title":"Mucosal Immunol"},{"key":"BFsrep41636_CR5","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1093\/intimm\/dxr001","volume":"23","author":"LA Zenewicz","year":"2011","unstructured":"Zenewicz, L. A. & Flavell, R. A. Recent advances in IL-22 biology. Int Immunol. 23, 159\u2013163 (2011).","journal-title":"Int Immunol"},{"key":"BFsrep41636_CR6","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/ni.2025","volume":"12","author":"GF Sonnenberg","year":"2011","unstructured":"Sonnenberg, G. F., Fouser, L. A. & Artis, D. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat Immunol. 12, 383\u2013390 (2011).","journal-title":"Nat Immunol"},{"key":"BFsrep41636_CR7","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1016\/j.intimp.2015.08.016","volume":"28","author":"N Xin","year":"2015","unstructured":"Xin, N., Namaka, M. P., Dou, C. & Zhang, Y. Exploring the role of interleukin-22 in neurological and autoimmune disorders. Int Immunopharmacol. 28, 1076\u20131083 (2015).","journal-title":"Int Immunopharmacol"},{"key":"BFsrep41636_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cellimm.2016.05.003","volume":"304","author":"Z Lu","year":"2016","unstructured":"Lu,, Z., Liu, R., Huang, E. & Chu, Y. MicroRNAs: New regulators of IL-22. Cell Immunol 304, 1\u20138 (2016).","journal-title":"Cell Immunol"},{"key":"BFsrep41636_CR9","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1038\/nm1651","volume":"13","author":"H Kebir","year":"2007","unstructured":"Kebir, H. et al. Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med. 13, 1173\u20131175 (2007).","journal-title":"Nat Med"},{"key":"BFsrep41636_CR10","doi-asserted-by":"publisher","first-page":"9511","DOI":"10.1073\/pnas.171303198","volume":"98","author":"W Xu","year":"2001","unstructured":"Xu, W. et al. A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist. Proc Natl Acad Sci USA. 98, 9511\u20139516 (2001).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep41636_CR11","doi-asserted-by":"publisher","first-page":"7090","DOI":"10.4049\/jimmunol.166.12.7090","volume":"166","author":"L Dumoutier","year":"2001","unstructured":"Dumoutier, L., Lejeune, D., Colau, D. & Renauld, J. C. Cloning and characterization of IL-22 binding protein, a natural antagonist of IL-10-related T cell-derived inducible factor\/IL-22. J Immunol. 166, 7090\u20137095 (2001).","journal-title":"J Immunol"},{"key":"BFsrep41636_CR12","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1002\/hep.20184","volume":"39","author":"S Radaeva","year":"2004","unstructured":"Radaeva, S., Sun, R., Pan, H. N., Hong, F. & Gao, B. Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation. Hepatology. 39, 1332\u20131342 (2004).","journal-title":"Hepatology"},{"key":"BFsrep41636_CR13","doi-asserted-by":"publisher","first-page":"G74","DOI":"10.1152\/ajpgi.00075.2009","volume":"298","author":"X Ren","year":"2010","unstructured":"Ren, X., Hu, B. & Colletti, L. M. IL-22 is involved in liver regeneration after hepatectomy. Am J Physiol Gastrointest Liver Physiol. 298, G74\u2013G80 (2010).","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"BFsrep41636_CR14","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1002\/hep.27629","volume":"61","author":"M Sertorio","year":"2015","unstructured":"Sertorio, M. et al. IL-22 and IL-22 binding protein (IL-22BP) regulate fibrosis and cirrhosis in hepatitis C virus and schistosome infections. Hepatology. 61, 1321\u20131331 (2015).","journal-title":"Hepatology"},{"key":"BFsrep41636_CR15","first-page":"2379","volume":"119","author":"MG Pitta","year":"2009","unstructured":"Pitta, M. G. et al. IL-17 and IL-22 are associated with protection against human kala azar caused by Leishmania donovani . J Clin Invest. 119, 2379\u20132387 (2009).","journal-title":"J Clin Invest"},{"key":"BFsrep41636_CR16","doi-asserted-by":"publisher","first-page":"e44153","DOI":"10.1371\/journal.pone.0044153","volume":"7","author":"P Wang","year":"2012","unstructured":"Wang, P. et al. IL-22 signaling contributes to West Nile encephalitis pathogenesis. PLoS One. 7, e44153 (2012).","journal-title":"PLoS One"},{"key":"BFsrep41636_CR17","doi-asserted-by":"crossref","unstructured":"Li, S., Yu, M., Li, H., Zhang, H. & Jiang, Y. IL-17 and IL-22 in cerebrospinal fluid and plasma are elevated in Guillain-Barre syndrome. Mediators Inflamm. 260473, 10.1155\/2012\/260473 (2012).","DOI":"10.1155\/2012\/260473"},{"key":"BFsrep41636_CR18","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/srep00020","volume":"1","author":"G Zhang","year":"2011","unstructured":"Zhang, G. et al. An SNP selection strategy identified IL-22 associating with susceptibility to tuberculosis in Chinese. Sci Rep. 1, 20, 10.1038\/srep00020 (2011).","journal-title":"Sci Rep"},{"key":"BFsrep41636_CR19","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1038\/jid.2014.5","volume":"134","author":"P Nikamo","year":"2014","unstructured":"Nikamo, P. et al. Genetic variants of the IL22 promoter associate to onset of psoriasis before puberty and increased IL-22 production in T cells. J Invest Dermatol. 134, 1535\u20131541 (2014).","journal-title":"J Invest Dermatol"},{"key":"BFsrep41636_CR20","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1007\/s00204-012-0818-2","volume":"86","author":"C Esser","year":"2012","unstructured":"Esser, C. Biology and function of the aryl hydrocarbon receptor: report of an international and interdisciplinary conference. Arch Toxicol. 86, 1323\u20131329 (2012).","journal-title":"Arch Toxicol."},{"key":"BFsrep41636_CR21","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.immuni.2013.08.002","volume":"39","author":"J Qiu","year":"2013","unstructured":"Qiu, J. et al. Group 3 innate lymphoid cells inhibit T-cell-mediated intestinal inflammation through aryl hydrocarbon receptor signaling and regulation of microflora. Immunity. 39, 386\u2013399 (2013).","journal-title":"Immunity"},{"key":"BFsrep41636_CR22","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1002\/eji.201040461","volume":"40","author":"JM Ramirez","year":"2010","unstructured":"Ramirez, J. M. et al. Activation of the aryl hydrocarbon receptor reveals distinct requirements for IL-22 and IL-17 production by human T helper cells. Eur J Immunol. 40, 450\u20132459 (2010).","journal-title":"Eur J Immunol"},{"key":"BFsrep41636_CR23","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1038\/ni.1770","volume":"10","author":"S Trifari","year":"2009","unstructured":"Trifari, S., Kaplan, C. D., Tran, E. H., Crellin, N. K. & Spits, H. Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. Nat Immunol. 10, 864\u2013871 (2009).","journal-title":"Nat Immunol"},{"key":"BFsrep41636_CR24","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/nature06881","volume":"453","author":"M Veldhoen","year":"2008","unstructured":"Veldhoen, M. et al. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature. 453, 106\u2013109 (2008).","journal-title":"Nature"},{"key":"BFsrep41636_CR25","doi-asserted-by":"publisher","first-page":"5943","DOI":"10.1073\/pnas.0911755107","volume":"107","author":"MS Alam","year":"2010","unstructured":"Alam, M. S. et al. Notch signaling drives IL-22 secretion in CD4+ T cells by stimulating the aryl hydrocarbon receptor. Proc Natl Acad Sci USA 107, 5943\u20135948 (2010).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep41636_CR26","doi-asserted-by":"publisher","first-page":"D539","DOI":"10.1093\/nar\/gkn814","volume":"37","author":"C Aurrecoechea","year":"2009","unstructured":"Aurrecoechea, C. et al. PlasmoDB: a functional genomic database for malaria parasites. Nucleic Acids Res. 37, D539\u2013D543 (2009).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep41636_CR27","doi-asserted-by":"publisher","first-page":"8393","DOI":"10.1073\/pnas.0801993105","volume":"105","author":"EK De Silva","year":"2008","unstructured":"De Silva, E. K. et al. Specific DNA-binding by apicomplexan AP2 transcription factors. Proc Natl Acad Sci USA 105, 8393\u20138398 (2008).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep41636_CR28","doi-asserted-by":"publisher","first-page":"207","DOI":"10.4269\/ajtmh.2001.64.207","volume":"64","author":"H Brown","year":"2001","unstructured":"Brown, H. et al. Blood-brain barrier function in cerebral malaria in Malawian children. Am J Trop Med. Hyg. 64, 207\u20132013 (2001).","journal-title":"Am J Trop Med. Hyg"},{"key":"BFsrep41636_CR29","doi-asserted-by":"publisher","first-page":"G827","DOI":"10.1152\/ajpgi.00513.2005","volume":"290","author":"S Brand","year":"2006","unstructured":"Brand, S. et al. IL-22 is increased in active Crohn\u2019s disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Am J Physiol Gastrointest Liver Physiol. 290, G827\u2013G838 (2006).","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"BFsrep41636_CR30","doi-asserted-by":"publisher","first-page":"7352","DOI":"10.1523\/JNEUROSCI.1002-05.2005","volume":"25","author":"MF Penet","year":"2005","unstructured":"Penet, M. F. et al. Imaging experimental cerebral malaria in vivo: significant role of ischemic brain edema. J Neurosci. 25, 7352\u20137358 (2005).","journal-title":"J Neurosci"},{"key":"BFsrep41636_CR31","doi-asserted-by":"publisher","first-page":"e27473","DOI":"10.1371\/journal.pone.0027473","volume":"6","author":"B Almolda","year":"2011","unstructured":"Almolda, B., Costa, M., Montoya, M., Gonzalez, B. & Castellano, B. Increase in Th17 and T-reg lymphocytes and decrease of IL22 correlate with the recovery phase of acute EAE in rat. PLoS One. 6, e27473, 10.1371\/journal.pone.0027473 (2011).","journal-title":"PLoS One"},{"key":"BFsrep41636_CR32","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1084\/jem.20092054","volume":"207","author":"GF Sonnenberg","year":"2010","unstructured":"Sonnenberg, G. F. et al. Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A. J Exp Med. 207, 1293\u20131305 (2010).","journal-title":"J Exp Med"},{"key":"BFsrep41636_CR33","doi-asserted-by":"publisher","first-page":"5263","DOI":"10.4049\/jimmunol.0902464","volume":"184","author":"K Guilloteau","year":"2010","unstructured":"Guilloteau, K. et al. Skin inflammation induced by the synergistic action of IL-17A, IL-22, oncostatin M, IL-1{alpha}, and TNF-{alpha} recapitulates some features of psoriasis. J Immunol. 184, 5263\u20135270 (2010).","journal-title":"J Immunol"},{"key":"BFsrep41636_CR34","doi-asserted-by":"crossref","unstructured":"Mastelic, B. et al. IL-22 Protects against liver pathology and lethality of an experimental blood-stage malaria infection. Front Immunol. 3, 10.3389\/fimmu.2012.00085 (2012).","DOI":"10.3389\/fimmu.2012.00085"},{"key":"BFsrep41636_CR35","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.cyto.2011.07.022","volume":"56","author":"WW Xing","year":"2011","unstructured":"Xing, W. W. et al. Hepatoprotective effects of IL-22 on fulminant hepatic failure induced by D-galactosamine and lipopolysaccharide in mice. Cytokine. 56, 174\u2013179 (2011).","journal-title":"Cytokine"},{"key":"BFsrep41636_CR36","doi-asserted-by":"publisher","first-page":"2828","DOI":"10.1002\/eji.201141291","volume":"41","author":"M Xu","year":"2011","unstructured":"Xu, M. et al. Regulation of the development of acute hepatitis by IL-23 through IL-22 and IL-17 production. Eur J Immunol. 41, 2828\u20132839 (2011).","journal-title":"Eur J Immunol"},{"key":"BFsrep41636_CR37","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.immuni.2007.07.023","volume":"27","author":"LA Zenewicz","year":"2007","unstructured":"Zenewicz, L. A. et al. Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity. 27, 647\u2013659 (2007).","journal-title":"Immunity"},{"key":"BFsrep41636_CR38","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.immuni.2004.07.007","volume":"21","author":"K Wolk","year":"2004","unstructured":"Wolk, K. et al. IL-22 increases the innate immunity of tissues. Immunity. 21, 241\u2013254 (2004).","journal-title":"Immunity"},{"key":"BFsrep41636_CR39","doi-asserted-by":"publisher","first-page":"e49778","DOI":"10.1371\/journal.pone.0049778","volume":"7","author":"F Burte","year":"2012","unstructured":"Burte, F. et al. Severe childhood malaria syndromes defined by plasma proteome profiles. PLoS One. 7, e49778, 10.1371\/journal.pone.0049778 (2012).","journal-title":"PLoS One"},{"key":"BFsrep41636_CR40","doi-asserted-by":"publisher","first-page":"3016","DOI":"10.1182\/blood-2012-10-461418","volume":"121","author":"F Burte","year":"2013","unstructured":"Burte, F. et al. Circulatory hepcidin is associated with the anti-inflammatory response but not with iron or anemic status in childhood malaria. Blood. 121, 3016\u20133022 (2013).","journal-title":"Blood"},{"key":"BFsrep41636_CR41","doi-asserted-by":"publisher","first-page":"e1004038","DOI":"10.1371\/journal.ppat.1004038","volume":"10","author":"J Bachmann","year":"2014","unstructured":"Bachmann, J. et al. Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria. PLoS Pathog. 10, e1004038, 10.1371\/journal.ppat.1004038 (2014).","journal-title":"PLoS Pathog"},{"key":"BFsrep41636_CR42","doi-asserted-by":"crossref","unstructured":"Severe malaria. World Health Organization. Trop Med Int Health 19, Suppl 1, 7\u2013131 (2014).","DOI":"10.1111\/tmi.12313_2"},{"key":"BFsrep41636_CR43","doi-asserted-by":"crossref","unstructured":"Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg. 94, Suppl 1:S1 (2000).","DOI":"10.1016\/S0035-9203(00)90300-6"},{"key":"BFsrep41636_CR44","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/s00251-015-0836-3","volume":"67","author":"S Cabantous","year":"2015","unstructured":"Cabantous, S. et al. Genotype combinations of two IL4 polymorphisms influencing IL-4 plasma levels are associated with different risks of severe malaria in the Malian population. Immunogenetics. 67, 283\u2013288 (2015).","journal-title":"Immunogenetics"},{"key":"BFsrep41636_CR45","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1086\/432484","volume":"192","author":"S Cabantous","year":"2005","unstructured":"Cabantous, S. et al. Evidence that interferon-gamma plays a protective role during cerebral malaria. J Infect Dis. 192, 854\u2013860 (2005).","journal-title":"J Infect Dis"},{"key":"BFsrep41636_CR46","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1086\/644600","volume":"200","author":"S Cabantous","year":"2009","unstructured":"Cabantous, S. et al. Genetic evidence for the aggravation of Plasmodium falciparum malaria by interleukin 4. J Infect Dis. 200, 1530\u20131539 (2009).","journal-title":"J Infect Dis"},{"key":"BFsrep41636_CR47","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1093\/hmg\/ddn118","volume":"17","author":"S Marquet","year":"2008","unstructured":"Marquet, S. et al. A functional promoter variant in IL12B predisposes to cerebral malaria. Hum Mol Genet. 17, 2190\u20132195 (2008).","journal-title":"Hum Mol Genet"},{"key":"BFsrep41636_CR48","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1128\/IAI.00671-15","volume":"84","author":"S Marquet","year":"2016","unstructured":"Marquet, S. et al. The IL17F and IL17RA genetic variants increase risk of cerebral malaria in two African populations. Infect Immun. 84, 590\u2013597 (2016).","journal-title":"Infect Immun"},{"key":"BFsrep41636_CR49","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1038\/sj.ejhg.5200625","volume":"9","author":"S Horvath","year":"2001","unstructured":"Horvath, S., Xu, X. & Laird, N. M. The family based association test method: strategies for studying general genotype\u2013phenotype associations. Eur J Hum Genet. 9, 301\u2013306 (2001).","journal-title":"Eur J Hum Genet"},{"key":"BFsrep41636_CR50","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/gepi.10307","volume":"26","author":"HJ Cordell","year":"2004","unstructured":"Cordell, H. J., Barratt, B. J. & Clayton, D. G. Case\/pseudocontrol analysis in genetic association studies: A unified framework for detection of genotype and haplotype associations, gene-gene and gene-environment interactions, and parent-of-origin effects. Genet Epidemiol. 26, 167\u2013185 (2004).","journal-title":"Genet Epidemiol"},{"key":"BFsrep41636_CR51","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1093\/infdis\/jiu140","volume":"210","author":"A Sabri","year":"2014","unstructured":"Sabri, A. et al. Association study of genes controlling IL-12-dependent IFN-gamma immunity: STAT4 alleles increase risk of pulmonary tuberculosis in Morocco. J Infect Dis. 210, 611\u2013618 (2014).","journal-title":"J Infect Dis"},{"key":"BFsrep41636_CR52","doi-asserted-by":"publisher","first-page":"e5","DOI":"10.1371\/journal.pcbi.0040005","volume":"4","author":"MC Andersen","year":"2008","unstructured":"Andersen, M. C. et al. In silico detection of sequence variations modifying transcriptional regulation. PLoS Comput Biol. 4, e5, 10.1371\/journal.pcbi.0040005 (2008).","journal-title":"PLoS Comput Biol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep41636.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep41636","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep41636.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T00:33:56Z","timestamp":1692664436000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep41636"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,31]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,3,14]]}},"alternative-id":["BFsrep41636"],"URL":"https:\/\/doi.org\/10.1038\/srep41636","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,31]]},"assertion":[{"value":"28 September 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 December 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 January 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"41636"}}