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A Functional IL22 Polymorphism (rs2227473) Is Associated with Predisposition to Childhood Cerebral Malaria

S. Marquet 1, * Ianina Conte 2 Belco Poudiougou 3 Laurent Argiro 1 Hélia Dessein 1 Charlène Couturier 1 Florence Burte 2 Aboubacar A Oumar 4 Biobele J Brown 5, 6, 7 Abdoualye Traore 3 Nathaniel K Afolabi 5 Abdoulaye Barry Samuel Omokhodion 5, 7 Wuraola A Shokunbi 6, 7 Olugbemiro Sodeinde 2, 5, 6, 7 Ogobara Doumbo 3 Delmiro Fernandez-Reyes 2, 5, 6, 7, * Alain J Dessein 1
* Corresponding author
1 GIMP - Génétique et immunologie des maladies parasitaires
2 Department of Computer Science
3 Department of Epidemiology of Parasitic Diseases [Bamako, Mali]
4 Centre des Oeuvres Universitaires [Bamako, Mali]
5 College of Medicine - Department of Pediatrics [Ibadan, Nigeria]
6 College of Medicine - Department of Hematology [Ibadan, Nigeria]
7 College of Medicine - Childhood Malaria Research Group [Ibadan, Nigeria]
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.
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S. Marquet, Ianina Conte, Belco Poudiougou, Laurent Argiro, Hélia Dessein, et al.. A Functional IL22 Polymorphism (rs2227473) Is Associated with Predisposition to Childhood Cerebral Malaria. Scientific Reports, Nature Publishing Group, 2017, 7, pp.41636. ⟨10.1038/srep41636⟩. ⟨hal-01595967⟩

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