title: Interferon regulatory factor-1 polymorphisms are associated with the control of Plasmodium falciparum infection.
abstract: We describe the haplotypic structure of the interferon regulatory factor-1 (IRF-1) locus in two West African ethnic groups, Fulani and Mossi, that differ in their susceptibility and immune response to Plasmodium falciparum malaria. Both populations showed significant associations between IRF-1 polymorphisms and carriage of P. falciparum infection, with different patterns of association that may reflect their different haplotypic architecture. Genetic variation at this locus does not therefore account for the Fulani-specific resistance to malaria while it could contribute to parasite clearance's ability in populations living in endemic areas. We then conducted a case-control study of three haplotype-tagging single nucleotide polymorphisms (htSNPs) in 370 hospitalised malaria patients (160 severe and 210 uncomplicated) and 410 healthy population controls, all from the Mossi ethnic group. All three htSNPs showed correlation with blood infection levels in malaria patients, and the rs10065633 polymorphism was associated with severe disease (P=0.02). These findings provide the first evidence of the involvement in malaria susceptibility of a specific locus within the 5q31 region, previously shown to be linked with P. falciparum infection levels.
authors.affiliation: Dipartimento di Scienze di Sanità Pubblica, Sezione di Parassitologia, Università di Roma 'La Sapienza', Rome, Italy. david.modiano@uniroma1.it
authors.forename: V D
authors.initials: VD
authors.lastname: Mangano
authors.forename: G
authors.initials: G
authors.lastname: Luoni
authors.forename: K A
authors.initials: KA
authors.lastname: Rockett
authors.forename: B S
authors.initials: BS
authors.lastname: Sirima
authors.forename: A
authors.initials: A
authors.lastname: Konaté
authors.forename: J
authors.initials: J
authors.lastname: Forton
authors.forename: T G
authors.initials: TG
authors.lastname: Clark
authors.forename: G
authors.initials: G
authors.lastname: Bancone
authors.forename: E
authors.initials: E
authors.lastname: Sadighi Akha
authors.forename: E S
authors.initials: ES
authors.lastname: Akha
authors.forename: D P
authors.initials: DP
authors.lastname: Kwiatkowski
authors.forename: D
authors.initials: D
authors.lastname: Modiano
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002050:Burkina Faso / Q000453:epidemiology / Q000208:ethnology; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics*; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D050856:Interferon Regulatory Factor-1