A variant in the gene FUT9 is associated with susceptibility to placental malaria infection

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 SNP located in the gene FUT9, rs3811070, was significantly associated with placental malaria infection (OR = 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.

This work was supported by grant SAF-2007-63171 awarded by Ministerio de Educación y Ciencia (Spain) to JB and the CIBERESP (CIBER of Epidemiology and Public Health, Ministry of Health). Funds were also obtained from Direcció General de Recerca of Generalitat de Catalunya (Grup de Recerca Consolidat 2005SGR/00608) and from Banco de Bilbao, Vizcaya, Argentaria Foundation (grant number BBVA 02-0). The CISM receives core support from the Spanish Agency for International Cooperation and Development (AECID). All the genotyping was provided by the Spanish "Centro Nacional de Genotipado" (CEGEN; www.cegen.org); Support for computations was provided by the National Institute for Bioinformatics (www.inab.org); both are platforms of Genoma España. MS is supported by a PhD fellowship from the Programa de becas FPU del Ministerio de Educación y Ciencia, Spain (AP2005-3982).