title: A variant in the gene FUT9 is associated with susceptibility to placental malaria infection.
abstract: Malaria in pregnancy forms a substantial part of the worldwide burden of malaria, with an estimated annual death toll of up to 200 000 infants, as well as increased maternal morbidity and mortality. Studies of genetic susceptibility to malaria have so far focused on infant malaria, with only a few studies investigating the genetic basis of placental malaria, focusing only on a limited number of candidate genes. The aim of this study therefore was to identify novel host genetic factors involved in placental malaria infection. To this end we carried out a nested case-control study on 180 Mozambican pregnant women with placental malaria infection, and 180 controls within an intervention trial of malaria prevention. We genotyped 880 SNPs in a set of 64 functionally related genes involved in glycosylation and innate immunity. A single nucleotide polymorphism (SNP) located in the gene FUT9, rs3811070, was significantly associated with placental malaria infection (odds ratio = 2.31, permutation P-value=0.028). Haplotypic analysis revealed a similarly strong association of a common haplotype of four SNPs including rs3811070. FUT9 codes for a fucosyl-transferase that is catalyzing the last step in the biosynthesis of the Lewis-x antigen, which forms part of the Lewis blood group-related antigens. These results therefore suggest an involvement of this antigen in the pathogenesis of placental malaria infection.
authors.affiliation: Institute of Evolutionary Biology (UPF-CSIC), CEXS-UPF-PRBB, Barcelona, Catalonia, Spain.
authors.forename: Martin
authors.initials: M
authors.lastname: Sikora
authors.forename: Anna
authors.initials: A
authors.lastname: Ferrer-Admetlla
authors.forename: Hafid
authors.initials: H
authors.lastname: Laayouni
authors.forename: Clara
authors.initials: C
authors.lastname: Menendez
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mayor
authors.forename: Azucena
authors.initials: A
authors.lastname: Bardaji
authors.forename: Betuel
authors.initials: B
authors.lastname: Sigauque
authors.forename: Inacio
authors.initials: I
authors.lastname: Mandomando
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Alonso
authors.forename: Jaume
authors.initials: J
authors.lastname: Bertranpetit
authors.forename: Ferran
authors.initials: F
authors.lastname: Casals
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D004198:Disease Susceptibility; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics* / Q000378:metabolism; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008288:Malaria / Q000235:genetics* / Q000469:parasitology; D008969:Molecular Sequence Data; D009073:Mozambique; D010922:Placenta Diseases / Q000235:genetics / Q000469:parasitology*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000235:genetics* / Q000469:parasitology; D055815:Young Adult
chemical_list: C519500:FUT9 protein, human; D005647:Fucosyltransferases