Natural selection of FLT1 alleles and their association with malaria resistance in utero

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dc.contributor.authorMutabingwa, Theonest K.
dc.date.accessioned2020-03-11T04:28:27Z
dc.date.available2020-03-11T04:28:27Z
dc.date.issued2008
dc.description.abstractPlacental malaria (PM) caused by Plasmodium falciparum contributes significantly to infant mortality in sub-Saharan Africa and is associated with pregnancy loss. We hypothesized that fetal genes that modify PM would be associated with fetal fitness. During PM, placental trophoblasts produce soluble fms-like tyrosine kinase 1 (sFlt1), also known as soluble VEGF receptor 1, an angiogenesis inhibitor associated with preeclampsia. Here we present a study examining the genotype of the fms-related tyrosine kinase 1 (FLT1) 3′ UTR in Tanzanian mother–infant pairs. First-time mothers suffer the most PM, and newborn FLT1 genotype distribution differed by birth order, with newborns of first-time mothers outside of Hardy–Weinberg equilibrium (HWE) during peak PM season. Among first-time but not other mothers, maternal FLT1 genotype was associated with a history of prior pregnancy loss. During PM, newborn FLT1 genotype was associated with low birth weight and placental inflammatory gene expression. FLT1 genotype was also associated with Flt1 levels among study subjects and in vitro. Thus, FLT1 variants confer fetal fitness in utero and are associated with the maternal immune response during PM. This indicates that FLT1 is under natural selection in a malaria endemic area and that human exposure to malaria can influence the evolutionary genetics of the maternal-fetal relationship.en_US
dc.identifier.citationMuehlenbachs, A., Fried, M., Lachowitzer, J., Mutabingwa, T.K. and Duffy, P.E., 2008. Natural selection of FLT1 alleles and their association with malaria resistance in utero. Proceedings of the National Academy of Sciences, 105(38), pp.14488-14491.en_US
dc.identifier.otherhttps://doi.org/10.1073/pnas.0803657105
dc.identifier.urihttp://hdl.handle.net/123456789/318
dc.language.isoenen_US
dc.publisherNational Academy of Sciencesen_US
dc.subjectAngiogenesisen_US
dc.subjectParasitologyen_US
dc.subjectPregnancyen_US
dc.titleNatural selection of FLT1 alleles and their association with malaria resistance in uteroen_US
dc.typePresentationen_US

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