SidaGhanaV1, Main, Exploration, bibRecord, 000848

A −436C>A Polymorphism in the Human FAS Gene Promoter Associated with Severe Childhood Malaria

Identifieur interne : 000848 ( Main/Exploration ); précédent : 000847; suivant : 000849

A −436C>A Polymorphism in the Human FAS Gene Promoter Associated with Severe Childhood Malaria

Auteurs : Kathrin Schuldt [Allemagne] ; Cosima C. Kretz [Allemagne] ; Christian Timmann [Allemagne] ; Jürgen Sievertsen [Allemagne] ; Christa Ehmen [Allemagne] ; Claudia Esser [Allemagne] ; Wibke Loag [Allemagne] ; Daniel Ansong [Ghana] ; Carmen Dering [Allemagne] ; Jennifer Evans [Allemagne] ; Andreas Ziegler [Allemagne] ; Jürgen May [Allemagne] ; Peter H. Krammer [Allemagne] ; Tsiri Agbenyega [Ghana] ; Rolf D. Horstmann [Allemagne]

Source :

PLoS Genetics [ 1553-7390 ] ; 2011.

RBID : PMC:3098189

Abstract

Human genetics and immune responses are considered to critically influence the outcome of malaria infections including life-threatening syndromes caused by Plasmodium falciparum. An important role in immune regulation is assigned to the apoptosis-signaling cell surface receptor CD95 (Fas, APO-1), encoded by the gene FAS. Here, a candidate-gene association study including variant discovery at the FAS gene locus was carried out in a case-control group comprising 1,195 pediatric cases of severe falciparum malaria and 769 unaffected controls from a region highly endemic for malaria in Ghana, West Africa. We found the A allele of c.−436C>A (rs9658676) located in the promoter region of FAS to be significantly associated with protection from severe childhood malaria (odds ratio 0.71, 95% confidence interval 0.58–0.88, p_empirical = 0.02) and confirmed this finding in a replication group of 1,412 additional severe malaria cases and 2,659 community controls from the same geographic area. The combined analysis resulted in an odds ratio of 0.71 (95% confidence interval 0.62–0.80, p = 1.8×10⁻⁷, n = 6035). The association applied to c.−436AA homozygotes (odds ratio 0.47, 95% confidence interval 0.36–0.60) and to a lesser extent to c.−436AC heterozygotes (odds ratio 0.73, 95% confidence interval 0.63–0.84), and also to all phenotypic subgroups studied, including severe malaria anemia, cerebral malaria, and other malaria complications. Quantitative FACS analyses assessing CD95 surface expression of peripheral blood mononuclear cells of naïve donors showed a significantly higher proportion of CD69⁺CD95⁺ cells among persons homozygous for the protective A allele compared to AC heterozygotes and CC homozygotes, indicating a functional role of the associated CD95 variant, possibly in supporting lymphocyte apoptosis.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098189

DOI: 10.1371/journal.pgen.1002066
PubMed: 21625619
PubMed Central: 3098189

Affiliations:

Le document en format XML

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 Gene Promoter Associated with Severe Childhood Malaria</title>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A −436C>A Polymorphism in the Human <italic>FAS</italic>
 Gene Promoter Associated with Severe Childhood Malaria</title>
<author><name sortKey="Schuldt, Kathrin" sort="Schuldt, Kathrin" uniqKey="Schuldt K" first="Kathrin" last="Schuldt">Kathrin Schuldt</name>
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</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg</wicri:regionArea>
<placeName><settlement type="city">Hambourg</settlement>
<region type="land" nuts="2">Hambourg</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Institute of Medical Biometry and Statistics, University at Lübeck, University Hospital Schleswig-Holstein, Lübeck, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Medical Biometry and Statistics, University at Lübeck, University Hospital Schleswig-Holstein, Lübeck</wicri:regionArea>
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<wicri:noRegion>Lübeck</wicri:noRegion>
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<author><name sortKey="Kretz, Cosima C" sort="Kretz, Cosima C" uniqKey="Kretz C" first="Cosima C." last="Kretz">Cosima C. Kretz</name>
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</nlm:aff>
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<author><name sortKey="Timmann, Christian" sort="Timmann, Christian" uniqKey="Timmann C" first="Christian" last="Timmann">Christian Timmann</name>
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</nlm:aff>
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<author><name sortKey="Ehmen, Christa" sort="Ehmen, Christa" uniqKey="Ehmen C" first="Christa" last="Ehmen">Christa Ehmen</name>
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<author><name sortKey="Esser, Claudia" sort="Esser, Claudia" uniqKey="Esser C" first="Claudia" last="Esser">Claudia Esser</name>
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</nlm:aff>
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<author><name sortKey="Loag, Wibke" sort="Loag, Wibke" uniqKey="Loag W" first="Wibke" last="Loag">Wibke Loag</name>
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</nlm:aff>
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<author><name sortKey="Ansong, Daniel" sort="Ansong, Daniel" uniqKey="Ansong D" first="Daniel" last="Ansong">Daniel Ansong</name>
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</nlm:aff>
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<author><name sortKey="Dering, Carmen" sort="Dering, Carmen" uniqKey="Dering C" first="Carmen" last="Dering">Carmen Dering</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Institute of Medical Biometry and Statistics, University at Lübeck, University Hospital Schleswig-Holstein, Lübeck, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Medical Biometry and Statistics, University at Lübeck, University Hospital Schleswig-Holstein, Lübeck</wicri:regionArea>
<wicri:noRegion>Lübeck</wicri:noRegion>
<wicri:noRegion>Lübeck</wicri:noRegion>
<wicri:noRegion>Lübeck</wicri:noRegion>
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<author><name sortKey="Evans, Jennifer" sort="Evans, Jennifer" uniqKey="Evans J" first="Jennifer" last="Evans">Jennifer Evans</name>
<affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg</wicri:regionArea>
<placeName><settlement type="city">Hambourg</settlement>
<region type="land" nuts="2">Hambourg</region>
</placeName>
</affiliation>
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<author><name sortKey="Ziegler, Andreas" sort="Ziegler, Andreas" uniqKey="Ziegler A" first="Andreas" last="Ziegler">Andreas Ziegler</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Institute of Medical Biometry and Statistics, University at Lübeck, University Hospital Schleswig-Holstein, Lübeck, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Medical Biometry and Statistics, University at Lübeck, University Hospital Schleswig-Holstein, Lübeck</wicri:regionArea>
<wicri:noRegion>Lübeck</wicri:noRegion>
<wicri:noRegion>Lübeck</wicri:noRegion>
<wicri:noRegion>Lübeck</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="May, Jurgen" sort="May, Jurgen" uniqKey="May J" first="Jürgen" last="May">Jürgen May</name>
<affiliation wicri:level="3"><nlm:aff id="aff4"><addr-line>Infectious Disease Epidemiology Group, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Infectious Disease Epidemiology Group, Bernhard Nocht Institute for Tropical Medicine, Hamburg</wicri:regionArea>
<placeName><settlement type="city">Hambourg</settlement>
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<author><name sortKey="Krammer, Peter H" sort="Krammer, Peter H" uniqKey="Krammer P" first="Peter H." last="Krammer">Peter H. Krammer</name>
<affiliation wicri:level="3"><nlm:aff id="aff3"><addr-line>Division of Immunogenetics, German Cancer Research Centre, Heidelberg, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Immunogenetics, German Cancer Research Centre, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Agbenyega, Tsiri" sort="Agbenyega, Tsiri" uniqKey="Agbenyega T" first="Tsiri" last="Agbenyega">Tsiri Agbenyega</name>
<affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana</addr-line>
</nlm:aff>
<country xml:lang="fr">Ghana</country>
<wicri:regionArea>School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi</wicri:regionArea>
<wicri:noRegion>Kumasi</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Horstmann, Rolf D" sort="Horstmann, Rolf D" uniqKey="Horstmann R" first="Rolf D." last="Horstmann">Rolf D. Horstmann</name>
<affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg</wicri:regionArea>
<placeName><settlement type="city">Hambourg</settlement>
<region type="land" nuts="2">Hambourg</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS Genetics</title>
<idno type="ISSN">1553-7390</idno>
<idno type="eISSN">1553-7404</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Human genetics and immune responses are considered to critically influence the outcome of malaria infections including life-threatening syndromes caused by <italic>Plasmodium falciparum</italic>
. An important role in immune regulation is assigned to the apoptosis-signaling cell surface receptor CD95 (Fas, APO-1), encoded by the gene <italic>FAS</italic>
. Here, a candidate-gene association study including variant discovery at the <italic>FAS</italic>
 gene locus was carried out in a case-control group comprising 1,195 pediatric cases of severe falciparum malaria and 769 unaffected controls from a region highly endemic for malaria in Ghana, West Africa. We found the A allele of c.−436C>A (rs9658676) located in the promoter region of <italic>FAS</italic>
 to be significantly associated with protection from severe childhood malaria (odds ratio 0.71, 95% confidence interval 0.58–0.88, p<sub>empirical</sub>
 = 0.02) and confirmed this finding in a replication group of 1,412 additional severe malaria cases and 2,659 community controls from the same geographic area. The combined analysis resulted in an odds ratio of 0.71 (95% confidence interval 0.62–0.80, p = 1.8×10<sup>−7</sup>
, n = 6035). The association applied to c.−436AA homozygotes (odds ratio 0.47, 95% confidence interval 0.36–0.60) and to a lesser extent to c.−436AC heterozygotes (odds ratio 0.73, 95% confidence interval 0.63–0.84), and also to all phenotypic subgroups studied, including severe malaria anemia, cerebral malaria, and other malaria complications. Quantitative FACS analyses assessing CD95 surface expression of peripheral blood mononuclear cells of naïve donors showed a significantly higher proportion of CD69<sup>+</sup>
CD95<sup>+</sup>
 cells among persons homozygous for the protective A allele compared to AC heterozygotes and CC homozygotes, indicating a functional role of the associated CD95 variant, possibly in supporting lymphocyte apoptosis.</p>
</div>
</front>
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<author><name sortKey="Bresolin, N" uniqKey="Bresolin N">N Bresolin</name>
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<author><name sortKey="Fahrig Faissner, A" uniqKey="Fahrig Faissner A">A Fahrig-Faissner</name>
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<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Ziegler, A" uniqKey="Ziegler A">A Ziegler</name>
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</biblStruct>
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<biblStruct><analytic><author><name sortKey="Bagos, Pg" uniqKey="Bagos P">PG Bagos</name>
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<author><name sortKey="Poland, Ga" uniqKey="Poland G">GA Poland</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Abecasis, Gr" uniqKey="Abecasis G">GR Abecasis</name>
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<author><name sortKey="Cardon, Lr" uniqKey="Cardon L">LR Cardon</name>
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</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Ghana</li>
</country>
<region><li>Bade-Wurtemberg</li>
<li>District de Karlsruhe</li>
<li>Hambourg</li>
</region>
<settlement><li>Hambourg</li>
<li>Heidelberg</li>
</settlement>
</list>
<tree><country name="Allemagne"><region name="Hambourg"><name sortKey="Schuldt, Kathrin" sort="Schuldt, Kathrin" uniqKey="Schuldt K" first="Kathrin" last="Schuldt">Kathrin Schuldt</name>
</region>
<name sortKey="Dering, Carmen" sort="Dering, Carmen" uniqKey="Dering C" first="Carmen" last="Dering">Carmen Dering</name>
<name sortKey="Ehmen, Christa" sort="Ehmen, Christa" uniqKey="Ehmen C" first="Christa" last="Ehmen">Christa Ehmen</name>
<name sortKey="Esser, Claudia" sort="Esser, Claudia" uniqKey="Esser C" first="Claudia" last="Esser">Claudia Esser</name>
<name sortKey="Evans, Jennifer" sort="Evans, Jennifer" uniqKey="Evans J" first="Jennifer" last="Evans">Jennifer Evans</name>
<name sortKey="Horstmann, Rolf D" sort="Horstmann, Rolf D" uniqKey="Horstmann R" first="Rolf D." last="Horstmann">Rolf D. Horstmann</name>
<name sortKey="Krammer, Peter H" sort="Krammer, Peter H" uniqKey="Krammer P" first="Peter H." last="Krammer">Peter H. Krammer</name>
<name sortKey="Kretz, Cosima C" sort="Kretz, Cosima C" uniqKey="Kretz C" first="Cosima C." last="Kretz">Cosima C. Kretz</name>
<name sortKey="Loag, Wibke" sort="Loag, Wibke" uniqKey="Loag W" first="Wibke" last="Loag">Wibke Loag</name>
<name sortKey="May, Jurgen" sort="May, Jurgen" uniqKey="May J" first="Jürgen" last="May">Jürgen May</name>
<name sortKey="Schuldt, Kathrin" sort="Schuldt, Kathrin" uniqKey="Schuldt K" first="Kathrin" last="Schuldt">Kathrin Schuldt</name>
<name sortKey="Sievertsen, Jurgen" sort="Sievertsen, Jurgen" uniqKey="Sievertsen J" first="Jürgen" last="Sievertsen">Jürgen Sievertsen</name>
<name sortKey="Timmann, Christian" sort="Timmann, Christian" uniqKey="Timmann C" first="Christian" last="Timmann">Christian Timmann</name>
<name sortKey="Timmann, Christian" sort="Timmann, Christian" uniqKey="Timmann C" first="Christian" last="Timmann">Christian Timmann</name>
<name sortKey="Ziegler, Andreas" sort="Ziegler, Andreas" uniqKey="Ziegler A" first="Andreas" last="Ziegler">Andreas Ziegler</name>
</country>
<country name="Ghana"><noRegion><name sortKey="Ansong, Daniel" sort="Ansong, Daniel" uniqKey="Ansong D" first="Daniel" last="Ansong">Daniel Ansong</name>
</noRegion>
<name sortKey="Agbenyega, Tsiri" sort="Agbenyega, Tsiri" uniqKey="Agbenyega T" first="Tsiri" last="Agbenyega">Tsiri Agbenyega</name>
</country>
</tree>
</affiliations>
</record>

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       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a SidaGhanaV1

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Data generation: Tue Nov 7 18:07:38 2017. Site generation: Tue Mar 5 15:01:57 2024

Le SIDA au Ghana (serveur d'exploration)

A −436C>A Polymorphism in the Human FAS Gene Promoter Associated with Severe Childhood Malaria

A −436C>A Polymorphism in the Human FAS Gene Promoter Associated with Severe Childhood Malaria

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	Le SIDA au Ghana (serveur d'exploration)
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.