title: A Functional IL22 Polymorphism (rs2227473) Is Associated with Predisposition to Childhood Cerebral Malaria.
abstract: Cerebral malaria (CM) is a severe complication of Plasmodium falciparum 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 (n = 46) of IL22 and IL22RA2 were associated with CM in children from Nigeria and Mali. Two SNPs of IL22, rs1012356 (P = 0.016, OR = 2.12) and rs2227476 (P = 0.007, OR = 2.08) were independently associated with CM in a sample of 115 Nigerian children with CM and 160 controls. The association with rs2227476 (P = 0.01) 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, (P = 0.004, OR = 1.55). 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.
authors.affiliation: Aix-Marseille University, INSERM, GIMP, Labex ParaFrap, Marseille, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marquet
authors.affiliation: Department of Computer Science, Faculty of Engineering Sciences, University College London, Gower Street, London, WCE2 6BT, United Kingdom.
authors.forename: Ianina
authors.initials: I
authors.lastname: Conte
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Disease, Faculty of Medicine, USTTB, BP 1805, Bamako, Mali.
authors.forename: Belco
authors.initials: B
authors.lastname: Poudiougou
authors.affiliation: Aix-Marseille University, INSERM, GIMP, Labex ParaFrap, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Argiro
authors.affiliation: Aix-Marseille University, INSERM, GIMP, Labex ParaFrap, Marseille, France.
authors.forename: Hélia
authors.initials: H
authors.lastname: Dessein
authors.affiliation: Aix-Marseille University, INSERM, GIMP, Labex ParaFrap, Marseille, France.
authors.forename: Charlène
authors.initials: C
authors.lastname: Couturier
authors.affiliation: Department of Computer Science, Faculty of Engineering Sciences, University College London, Gower Street, London, WCE2 6BT, United Kingdom.
authors.forename: Florence
authors.initials: F
authors.lastname: Burté
authors.affiliation: Centre des Oeuvres Universitaires, University of Bamako, BP 1805, Bamako, Mali.
authors.forename: Aboubacar A
authors.initials: AA
authors.lastname: Oumar
authors.affiliation: Department of Pediatrics, College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.|Department of Hematology, College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.|Childhood Malaria Research Group, College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.
authors.forename: Biobele J
authors.initials: BJ
authors.lastname: Brown
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Disease, Faculty of Medicine, USTTB, BP 1805, Bamako, Mali.
authors.forename: Abdoualye
authors.initials: A
authors.lastname: Traore
authors.affiliation: Department of Pediatrics, College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.
authors.forename: Nathaniel K
authors.initials: NK
authors.lastname: Afolabi
authors.affiliation: Pediatric Wards, Gabriel Toure Hospital, Bamako, Mali.
authors.forename: Abdoulaye
authors.initials: A
authors.lastname: Barry
authors.affiliation: Department of Pediatrics, College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.|Childhood Malaria Research Group, College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.
authors.forename: Samuel
authors.initials: S
authors.lastname: Omokhodion
authors.affiliation: Department of Hematology, College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.|Childhood Malaria Research Group, College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.
authors.forename: Wuraola A
authors.initials: WA
authors.lastname: Shokunbi
authors.affiliation: Department of Computer Science, Faculty of Engineering Sciences, University College London, Gower Street, London, WCE2 6BT, United Kingdom.|Department of Pediatrics, College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.|Department of Hematology, College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.|Childhood Malaria Research Group, College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.
authors.forename: Olugbemiro
authors.initials: O
authors.lastname: Sodeinde
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Disease, Faculty of Medicine, USTTB, BP 1805, Bamako, Mali.
authors.forename: Ogobara
authors.initials: O
authors.lastname: Doumbo
authors.affiliation: Department of Computer Science, Faculty of Engineering Sciences, University College London, Gower Street, London, WCE2 6BT, United Kingdom.|Department of Pediatrics, College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.|Department of Hematology, College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.|Childhood Malaria Research Group, College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.
authors.forename: Delmiro
authors.initials: D
authors.lastname: Fernandez-Reyes
authors.affiliation: Aix-Marseille University, INSERM, GIMP, Labex ParaFrap, Marseille, France.
authors.forename: Alain J
authors.initials: AJ
authors.lastname: Dessein
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D015810:Linkage Disequilibrium; D016779:Malaria, Cerebral / Q000235:genetics* / Q000469:parasitology; D016778:Malaria, Falciparum / Q000235:genetics / Q000469:parasitology; D008297:Male; D009549:Nigeria; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D000097043:Interleukin-22