Natural Selection of FLT1 Alleles and Their Association with Malaria Resistance in utero

Placental 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 ... Ausführliche Beschreibung

1. Person: Muehlenbachs, Atis
Weitere Personen: Fried, Michal verfasserin; Lachowitzer, Jeff verfasserin; Mutabingwa, Theonest K. verfasserin; Duffy, Patrick E. verfasserin
Quelle: in Proceedings of the National Academy of Sciences of the United States of America Vol. 105, No. 38 (2008), p. 14488-14491
Weitere Artikel
Format: Online-Artikel
Sprache: English
Veröffentlicht: 2008
Beschreibung: Online-Ressource
Schlagworte: research-article
Angiogenesis
Parasitology
Pregnancy
Placenta
Plasmodium falciparum
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Anmerkung: Copyright: Copyright 2008 The National Academy of Sciences of the United States of America
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520 |a Placental 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. 
653 |a research-article 
653 |a Angiogenesis 
653 |a Parasitology 
653 |a Pregnancy 
653 |a Placenta 
653 |a Plasmodium falciparum 
700 1 |a Fried, Michal  |e verfasserin  |4 aut 
700 1 |a Lachowitzer, Jeff  |e verfasserin  |4 aut 
700 1 |a Mutabingwa, Theonest K.  |e verfasserin  |4 aut 
700 1 |a Duffy, Patrick E.  |e verfasserin  |4 aut 
773 0 8 |i in  |t Proceedings of the National Academy of Sciences of the United States of America  |d Washington, DC : National Acad. of Sciences  |g Vol. 105, No. 38 (2008), p. 14488-14491  |q 105:38<14488-14491  |w (DE-601)JST069399220  |x 0027-8424 
856 4 1 |u https://www.jstor.org/stable/25464256  |3 Volltext 
912 |a GBV_JSTOR 
951 |a AR 
952 |d 105  |j 2008  |e 38  |h 14488-14491 

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