title: The toll-like receptor 1 variant S248N influences placental malaria.
abstract: In malaria-endemic regions, Plasmodium falciparum infection in pregnancy is a predominant cause of maternal and infant morbidity and mortality. Primiparae are relatively immune-naïve and particularly prone. Innate immune recognition of P. falciparum is partly mediated by Toll-like receptors (TLRs), and single nucleotide polymorphisms (SNPs) of TLR-4 and -9 influence manifestation. Recognition via TLR-2, which functions as heterodimer with TLR-1 or TLR-6, appears to be essential but in previous studies from Ghana, functional TLR-2 SNPs were virtually absent. In the present study, we assessed two well characterized TLR-1 polymorphisms, rs4833095 (S248N) and rs5743618 (I602S), among 302 primiparous Ghanaian women, and analysed associations with P. falciparum infection and manifestation. The prevalence of the TLR-1 S248N variant was 20.5%, whereas the TLR-1 I602S variant was rare at 2%. Placental P. falciparum infection was observed in 78% of women heterozygous for the TLR-1 S248N SNP but in 63% of women with the respective wildtype (P=0.03). Furthermore, the odds of malaria-associated anaemia were more than doubled in TLR-1 S248N heterozygous women (P=0.03) although parasite densities did not differ. No differences in the rates of low birth weight and preterm delivery were observed. These data support that TLR-1 is involved in the recognition of P. falciparum and indicate its role in susceptibility to and manifestation of malaria in pregnancy.
authors.affiliation: Institute for Microbiology and Hygiene, Charité - University Medical Center, Dorotheenstrasse 96, 10117 Berlin, Germany. lutz.hamann@charite.de
authors.forename: Lutz
authors.initials: L
authors.lastname: Hamann
authors.forename: George
authors.initials: G
authors.lastname: Bedu-Addo
authors.forename: Teunis A
authors.initials: TA
authors.lastname: Eggelte
authors.forename: Ralf R
authors.initials: RR
authors.lastname: Schumann
authors.forename: Frank P
authors.initials: FP
authors.lastname: Mockenhaupt
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000235:genetics*; D010920:Placenta / Q000469:parasitology* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000453:epidemiology / Q000235:genetics*; D015995:Prevalence; D012694:Serine / Q000235:genetics; D051194:Toll-Like Receptor 1 / Q000235:genetics*; D055815:Young Adult
chemical_list: D051194:Toll-Like Receptor 1; D012694:Serine