Endothelial Protein C Receptor Gene Variants Not Associated with Severe Malaria in Ghanaian Children
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{"title"=>"Endothelial protein C receptor gene variants not associated with severe malaria in Ghanaian children", "type"=>"journal", "authors"=>[{"first_name"=>"Kathrin", "last_name"=>"Schuldt", "scopus_author_id"=>"6603823196"}, {"first_name"=>"Christa", "last_name"=>"Ehmen", "scopus_author_id"=>"16401605400"}, {"first_name"=>"Jennifer", "last_name"=>"Evans", "scopus_author_id"=>"55476169600"}, {"first_name"=>"Juergen", "last_name"=>"May", "scopus_author_id"=>"7402251838"}, {"first_name"=>"Daniel", "last_name"=>"Ansong", "scopus_author_id"=>"6506910959"}, {"first_name"=>"Juergen", "last_name"=>"Sievertsen", "scopus_author_id"=>"16178354200"}, {"first_name"=>"Birgit", "last_name"=>"Muntau", "scopus_author_id"=>"6506409673"}, {"first_name"=>"Gerd", "last_name"=>"Ruge", "scopus_author_id"=>"6508192192"}, {"first_name"=>"Tsiri", "last_name"=>"Agbenyega", "scopus_author_id"=>"6603394104"}, {"first_name"=>"Rolf D.", "last_name"=>"Horstmann", "scopus_author_id"=>"16420119300"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "sgr"=>"84919897841", "scopus"=>"2-s2.0-84919897841", "pui"=>"601058882", "doi"=>"10.1371/journal.pone.0115770", "pmid"=>"25541704"}, "id"=>"99104e13-54b7-3561-8bda-9babb24605ce", "abstract"=>"BACKGROUND: Two recent reports have identified the Endothelial Protein C Receptor (EPCR) as a key molecule implicated in severe malaria pathology. First, it was shown that EPCR in the human microvasculature mediates sequestration of Plasmodium falciparum-infected erythrocytes. Second, microvascular thrombosis, one of the major processes causing cerebral malaria, was linked to a reduction in EPCR expression in cerebral endothelial layers. It was speculated that genetic variation affecting EPCR functionality could influence susceptibility to severe malaria phenotypes, rendering PROCR, the gene encoding EPCR, a promising candidate for an association study.\\n\\nMETHODS: Here, we performed an association study including high-resolution variant discovery of rare and frequent genetic variants in the PROCR gene. The study group, which previously has proven to be a valuable tool for studying the genetics of malaria, comprised 1,905 severe malaria cases aged 1-156 months and 1,866 apparently healthy children aged 2-161 months from the Ashanti Region in Ghana, West Africa, where malaria is highly endemic. Association of genetic variation with severe malaria phenotypes was examined on the basis of single variants, reconstructed haplotypes, and rare variant analyses.\\n\\nRESULTS: A total of 41 genetic variants were detected in regulatory and coding regions of PROCR, 17 of which were previously unknown genetic variants. In association tests, none of the single variants, haplotypes or rare variants showed evidence for an association with severe malaria, cerebral malaria, or severe malaria anemia.\\n\\nCONCLUSION: Here we present the first analysis of genetic variation in the PROCR gene in the context of severe malaria in African subjects and show that genetic variation in the PROCR gene in our study population does not influence susceptibility to major severe malaria phenotypes.", "link"=>"http://www.mendeley.com/research/endothelial-protein-c-receptor-gene-variants-not-associated-severe-malaria-ghanaian-children", "reader_count"=>16, "reader_count_by_academic_status"=>{"Librarian"=>1, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>3, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Librarian"=>1, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>3, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>3, "Business, Management and Accounting"=>1, "Social Sciences"=>2, "Immunology and Microbiology"=>2, "Earth and Planetary Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Social Sciences"=>{"Social Sciences"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}}, "reader_count_by_country"=>{"Denmark"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1856463"], "description"=>"<p>Aff, affected individuals; CI, confidence interval; HWE, Hardy-Weinberg equilibrium; MAF, minor allele frequency; OR, odds ratio; unaff, unaffected individuals.</p>a<p>Results of logistic regression analyses assuming an additive mode of inheritance adjusted for gender, age, and ethnicity</p><p>Association tests of <i>PROCR</i> SNPs (MAF ≥1%) with severe malaria, cerebral malaria, and severe malaria anemia.</p>", "links"=>[], "tags"=>["microvasculature mediates sequestration", "association", "PROCR gene", "Endothelial Protein C Receptor Gene Variants", "gene encoding EPCR", "Endothelial Protein C Receptor", "Ghanaian Children BackgroundTwo", "variant", "malaria phenotypes"], "article_id"=>1280661, "categories"=>["Biological Sciences"], "users"=>["Kathrin Schuldt", "Christa Ehmen", "Jennifer Evans", "Juergen May", "Daniel Ansong", "Juergen Sievertsen", "Birgit Muntau", "Gerd Ruge", "Tsiri Agbenyega", "Rolf D. Horstmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0115770.t002", "stats"=>{"downloads"=>3, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_tests_of_PROCR_SNPs_MAF_1_with_severe_malaria_cerebral_malaria_and_severe_malaria_anemia_/1280661", "title"=>"Association tests of <i>PROCR</i> SNPs (MAF ≥1%) with severe malaria, cerebral malaria, and severe malaria anemia.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-12-26 03:38:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/1856462"], "description"=>"<p>AA, amino acid; Ex, exon; In, intron; MAF, minor allele frequency.</p>a<p>Reference sequence NCBI NM_006404.4.</p><p>Genetic variants in the <i>PROCR</i> gene found in 3,771 Ghanaian children.</p>", "links"=>[], "tags"=>["microvasculature mediates sequestration", "association", "PROCR gene", "Endothelial Protein C Receptor Gene Variants", "gene encoding EPCR", "Endothelial Protein C Receptor", "Ghanaian Children BackgroundTwo", "variant", "malaria phenotypes"], "article_id"=>1280660, "categories"=>["Biological Sciences"], "users"=>["Kathrin Schuldt", "Christa Ehmen", "Jennifer Evans", "Juergen May", "Daniel Ansong", "Juergen Sievertsen", "Birgit Muntau", "Gerd Ruge", "Tsiri Agbenyega", "Rolf D. Horstmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0115770.t001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genetic_variants_in_the_PROCR_gene_found_in_3_771_Ghanaian_children_/1280660", "title"=>"Genetic variants in the <i>PROCR</i> gene found in 3,771 Ghanaian children.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-12-26 03:38:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/1856467", "https://ndownloader.figshare.com/files/1856468"], "description"=>"<div><p>Background</p><p>Two recent reports have identified the Endothelial Protein C Receptor (EPCR) as a key molecule implicated in severe malaria pathology. First, it was shown that EPCR in the human microvasculature mediates sequestration of <i>Plasmodium falciparum</i>-infected erythrocytes. Second, microvascular thrombosis, one of the major processes causing cerebral malaria, was linked to a reduction in EPCR expression in cerebral endothelial layers. It was speculated that genetic variation affecting EPCR functionality could influence susceptibility to severe malaria phenotypes, rendering <i>PROCR</i>, the gene encoding EPCR, a promising candidate for an association study.</p><p>Methods</p><p>Here, we performed an association study including high-resolution variant discovery of rare and frequent genetic variants in the <i>PROCR</i> gene. The study group, which previously has proven to be a valuable tool for studying the genetics of malaria, comprised 1,905 severe malaria cases aged 1–156 months and 1,866 apparently healthy children aged 2–161 months from the Ashanti Region in Ghana, West Africa, where malaria is highly endemic. Association of genetic variation with severe malaria phenotypes was examined on the basis of single variants, reconstructed haplotypes, and rare variant analyses.</p><p>Results</p><p>A total of 41 genetic variants were detected in regulatory and coding regions of <i>PROCR</i>, 17 of which were previously unknown genetic variants. In association tests, none of the single variants, haplotypes or rare variants showed evidence for an association with severe malaria, cerebral malaria, or severe malaria anemia.</p><p>Conclusion</p><p>Here we present the first analysis of genetic variation in the <i>PROCR</i> gene in the context of severe malaria in African subjects and show that genetic variation in the <i>PROCR</i> gene in our study population does not influence susceptibility to major severe malaria phenotypes.</p></div>", "links"=>[], "tags"=>["microvasculature mediates sequestration", "association", "PROCR gene", "Endothelial Protein C Receptor Gene Variants", "gene encoding EPCR", "Endothelial Protein C Receptor", "Ghanaian Children BackgroundTwo", "variant", "malaria phenotypes"], "article_id"=>1280665, "categories"=>["Biological Sciences"], "users"=>["Kathrin Schuldt", "Christa Ehmen", "Jennifer Evans", "Juergen May", "Daniel Ansong", "Juergen Sievertsen", "Birgit Muntau", "Gerd Ruge", "Tsiri Agbenyega", "Rolf D. Horstmann"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0115770.s001", "https://dx.doi.org/10.1371/journal.pone.0115770.s002"], "stats"=>{"downloads"=>0, "page_views"=>36, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Endothelial_Protein_C_Receptor_Gene_Variants_Not_Associated_with_Severe_Malaria_in_Ghanaian_Children_/1280665", "title"=>"Endothelial Protein C Receptor Gene Variants Not Associated with Severe Malaria in Ghanaian Children", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-12-26 03:38:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/1856465"], "description"=>"<p>CMC, combined and multivariate collapsing; WSS, weighted sum statistic; VT, variable thresholds methods.</p>a<p>Adjusted for age, gender, and ethnic group.</p><p>PROCR rare variant analyses including SNPs with MAF ≤1%.</p>", "links"=>[], "tags"=>["microvasculature mediates sequestration", "association", "PROCR gene", "Endothelial Protein C Receptor Gene Variants", "gene encoding EPCR", "Endothelial Protein C Receptor", "Ghanaian Children BackgroundTwo", "variant", "malaria phenotypes"], "article_id"=>1280663, "categories"=>["Biological Sciences"], "users"=>["Kathrin Schuldt", "Christa Ehmen", "Jennifer Evans", "Juergen May", "Daniel Ansong", "Juergen Sievertsen", "Birgit Muntau", "Gerd Ruge", "Tsiri Agbenyega", "Rolf D. Horstmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0115770.t004", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PROCR_rare_variant_analyses_including_SNPs_with_MAF_8804_1_/1280663", "title"=>"PROCR rare variant analyses including SNPs with MAF ≤1%.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-12-26 03:38:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/1856464"], "description"=>"<p>Aff, affected individuals; unaff, unaffected individuals.</p>a<p>Refers to SNP number as designated in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115770#pone-0115770-t002\" target=\"_blank\">Table 2</a>.</p>b<p>Results of haplotypic-specific score tests adjusted for gender, age, and ethnicity assuming an additive mode of inheritance.</p>c<p>Simulation p-values are computed based on a permuted re-ordering of the trait and covariates in Haplo Stats <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115770#pone.0115770-Schaid1\" target=\"_blank\">[29]</a>.</p><p>Association tests of <i>PROCR</i> haplotypes with severe malaria, cerebral malaria, and severe malaria anemia.</p>", "links"=>[], "tags"=>["microvasculature mediates sequestration", "association", "PROCR gene", "Endothelial Protein C Receptor Gene Variants", "gene encoding EPCR", "Endothelial Protein C Receptor", "Ghanaian Children BackgroundTwo", "variant", "malaria phenotypes"], "article_id"=>1280662, "categories"=>["Biological Sciences"], "users"=>["Kathrin Schuldt", "Christa Ehmen", "Jennifer Evans", "Juergen May", "Daniel Ansong", "Juergen Sievertsen", "Birgit Muntau", "Gerd Ruge", "Tsiri Agbenyega", "Rolf D. Horstmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0115770.t003", "stats"=>{"downloads"=>3, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_tests_of_PROCR_haplotypes_with_severe_malaria_cerebral_malaria_and_severe_malaria_anemia_/1280662", "title"=>"Association tests of <i>PROCR</i> haplotypes with severe malaria, cerebral malaria, and severe malaria anemia.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-12-26 03:38:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/1856461"], "description"=>"<p>The plot was generated on the basis of SNPs (MAF ≥1%) in healthy control individuals. Grey-scale squares represent pairwise r<sup>2</sup> values ranging from 0–1.</p>", "links"=>[], "tags"=>["microvasculature mediates sequestration", "association", "PROCR gene", "Endothelial Protein C Receptor Gene Variants", "gene encoding EPCR", "Endothelial Protein C Receptor", "Ghanaian Children BackgroundTwo", "variant", "malaria phenotypes"], "article_id"=>1280659, "categories"=>["Biological Sciences"], "users"=>["Kathrin Schuldt", "Christa Ehmen", "Jennifer Evans", "Juergen May", "Daniel Ansong", "Juergen Sievertsen", "Birgit Muntau", "Gerd Ruge", "Tsiri Agbenyega", "Rolf D. Horstmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0115770.g001", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Linkage_disequilibrium_plot_of_the_PROCR_gene_locus_/1280659", "title"=>"Linkage disequilibrium plot of the <i>PROCR</i> gene locus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-26 03:38:11"}

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Relative Metric

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