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  1. Article ; Online: Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19.

    Spiering, Anna E / de Vries, Teun J

    Frontiers in immunology

    2021  Volume 12, Page(s) 756262

    Abstract: A male sex bias has emerged in the COVID-19 pandemic, fitting to the sex-biased pattern in other viral infections. Males are 2.84 times more often admitted to the ICU and mortality is 1.39 times higher as a result of COVID-19. Various factors play a role ...

    Abstract A male sex bias has emerged in the COVID-19 pandemic, fitting to the sex-biased pattern in other viral infections. Males are 2.84 times more often admitted to the ICU and mortality is 1.39 times higher as a result of COVID-19. Various factors play a role in this, and novel studies suggest that the gene-dose of Toll-Like Receptor (TLR) 7 could contribute to the sex-skewed severity. TLR7 is one of the crucial pattern recognition receptors for SARS-CoV-2 ssRNA and the gene-dose effect is caused by X chromosome inactivation (XCI) escape. Female immune cells with TLR7 XCI escape have biallelic TLR7 expression and produce more type 1 interferon (IFN) upon TLR7 stimulation. In COVID-19, TLR7 in plasmacytoid dendritic cells is one of the pattern recognition receptors responsible for IFN production and a delayed IFN response has been associated with immunopathogenesis and mortality. Here, we provide a hypothesis that females may be protected to some extend against severe COVID-19, due to the biallelic TLR7 expression, allowing them to mount a stronger and more protective IFN response early after infection. Studies exploring COVID-19 treatment via the TLR7-mediated IFN pathway should consider this sex difference. Various factors such as age, sex hormones and escape modulation remain to be investigated concerning the TLR7 gene-dose effect.
    MeSH term(s) COVID-19/drug therapy ; COVID-19/mortality ; COVID-19/pathology ; Chromosomes, Human, X/genetics ; Critical Care/statistics & numerical data ; Dendritic Cells/immunology ; Female ; Gene Dosage/genetics ; Humans ; Interferon Type I/biosynthesis ; Interferon Type I/immunology ; Male ; RNA, Viral/genetics ; Receptors, Pattern Recognition/genetics ; Receptors, Pattern Recognition/metabolism ; Risk Factors ; SARS-CoV-2/immunology ; Sex Factors ; Signal Transduction/immunology ; Toll-Like Receptor 7/genetics ; Toll-Like Receptor 7/metabolism ; X Chromosome Inactivation/genetics
    Chemical Substances Interferon Type I ; RNA, Viral ; Receptors, Pattern Recognition ; TLR7 protein, human ; Toll-Like Receptor 7
    Language English
    Publishing date 2021-11-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.756262
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: 2018 ESC/ESH Guidelines for the management of arterial hypertension.

    Williams, Bryan / Mancia, Giuseppe / Spiering, Wilko / Rosei, Enrico Agabiti / Azizi, Michel / Burnier, Michel / Clement, Denis L / Coca, Antonio / de Simone, Giovanni / Dominiczak, Anna / Kahan, Thomas / Mahfoud, Felix / Redon, Josep / Ruilope, Luis / Zanchetti, Alberto / Kerins, Mary / Kjeldsen, Sverre E / Kreutz, Reinhold / Laurent, Stephane /
    Lip, Gregory Y H / McManus, Richard / Narkiewicz, Krzysztof / Ruschitzka, Frank / Schmieder, Roland E / Shlyakhto, Evgeny / Tsioufis, Costas / Aboyans, Victor / Desormais, Ileana

    Kardiologia polska

    2019  Volume 77, Issue 2, Page(s) 71–159

    Title translation 2018 ESC/ESH Guidelines for the management of arterial hypertension.
    MeSH term(s) Antihypertensive Agents/therapeutic use ; Cardiology ; Disease Management ; Europe ; Female ; Humans ; Hypertension/diagnosis ; Hypertension/drug therapy ; Hypertension/etiology ; Hypertension/therapy ; Male ; Societies, Medical
    Chemical Substances Antihypertensive Agents
    Language Polish
    Publishing date 2019-02-22
    Publishing country Poland
    Document type Journal Article ; Practice Guideline
    ZDB-ID 411492-9
    ISSN 1897-4279 ; 0022-9032
    ISSN (online) 1897-4279
    ISSN 0022-9032
    DOI 10.5603/KP.2019.0018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: 2018 ESC/ESH Guidelines for the management of arterial hypertension.

    Williams, Bryan / Mancia, Giuseppe / Spiering, Wilko / Agabiti Rosei, Enrico / Azizi, Michel / Burnier, Michel / Clement, Denis L / Coca, Antonio / de Simone, Giovanni / Dominiczak, Anna / Kahan, Thomas / Mahfoud, Felix / Redon, Josep / Ruilope, Luis / Zanchetti, Alberto / Kerins, Mary / Kjeldsen, Sverre E / Kreutz, Reinhold / Laurent, Stephane /
    Lip, Gregory Y H / McManus, Richard / Narkiewicz, Krzysztof / Ruschitzka, Frank / Schmieder, Roland E / Shlyakhto, Evgeny / Tsioufis, Costas / Aboyans, Victor / Desormais, Ileana

    European heart journal

    2018  Volume 39, Issue 33, Page(s) 3021–3104

    Language English
    Publishing date 2018-08-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 603098-1
    ISSN 1522-9645 ; 0195-668X
    ISSN (online) 1522-9645
    ISSN 0195-668X
    DOI 10.1093/eurheartj/ehy339
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Linee guida ESC/ESH 2018 per la diagnosi e il trattamento dell’ipertensione arteriosa. Task Force per la Diagnosi e il Trattamento dell’Ipertensione Arteriosa della Società Europea di Cardiologia (ESC) e della Società Europea dell’Ipertensione Arteriosa (ESH).

    Williams, Bryan / Mancia, Giuseppe / Spiering, Wilko / Rosei, Enrico Agabiti / Azizi, Michel / Burnier, Michel / Clement, Denis L / Coca, Antonio / de Simone, Giovanni / Dominiczak, Anna / Kahan, Thomas / Mahfoud, Felix / Redon, Josep / Ruilope, Luis / Zanchetti, Alberto / Kerins, Mary / Kjeldsen, Sverre E / Kreutz, Reinhold / Laurent, Stephane /
    Lip, Gregory Y H / McManus, Richard / Narkiewicz, Krzysztof / Ruschitzka, Frank / Schmieder, Roland E / Shlyakhto, Evgeny / Tsioufis, Costas / Aboyans, Victor / Desormais, Ileana

    Giornale italiano di cardiologia (2006)

    2018  Volume 19, Issue 11 Suppl 1, Page(s) 3S–73S

    Title translation 2018 ESC/ESH Guidelines for the management of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH).
    MeSH term(s) Antihypertensive Agents/administration & dosage ; Blood Pressure ; Blood Pressure Determination/methods ; Europe ; Humans ; Hypertension/diagnosis ; Hypertension/therapy
    Chemical Substances Antihypertensive Agents
    Language Italian
    Publishing date 2018-12-06
    Publishing country Italy
    Document type Journal Article ; Practice Guideline
    ZDB-ID 2272414-X
    ISSN 1972-6481 ; 1827-6806
    ISSN (online) 1972-6481
    ISSN 1827-6806
    DOI 10.1714/3026.30245
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension.

    Williams, Bryan / Mancia, Giuseppe / Spiering, Wilko / Agabiti Rosei, Enrico / Azizi, Michel / Burnier, Michel / Clement, Denis L / Coca, Antonio / de Simone, Giovanni / Dominiczak, Anna / Kahan, Thomas / Mahfoud, Felix / Redon, Josep / Ruilope, Luis / Zanchetti, Alberto / Kerins, Mary / Kjeldsen, Sverre E / Kreutz, Reinhold / Laurent, Stephane /
    Lip, Gregory Y H / McManus, Richard / Narkiewicz, Krzysztof / Ruschitzka, Frank / Schmieder, Roland E / Shlyakhto, Evgeny / Tsioufis, Costas / Aboyans, Victor / Desormais, Ileana

    Journal of hypertension

    2018  Volume 36, Issue 10, Page(s) 1953–2041

    Abstract: Document reviewers: Guy De Backer (ESC Review Co-ordinator) (Belgium), Anthony M. Heagerty (ESH Review Co-ordinator) (UK), Stefan Agewall (Norway), Murielle Bochud (Switzerland), Claudio Borghi (Italy), Pierre Boutouyrie (France), Jana Brguljan ( ... ...

    Abstract : Document reviewers: Guy De Backer (ESC Review Co-ordinator) (Belgium), Anthony M. Heagerty (ESH Review Co-ordinator) (UK), Stefan Agewall (Norway), Murielle Bochud (Switzerland), Claudio Borghi (Italy), Pierre Boutouyrie (France), Jana Brguljan (Slovenia), Héctor Bueno (Spain), Enrico G. Caiani (Italy), Bo Carlberg (Sweden), Neil Chapman (UK), Renata Cifkova (Czech Republic), John G. F. Cleland (UK), Jean-Philippe Collet (France), Ioan Mircea Coman (Romania), Peter W. de Leeuw (The Netherlands), Victoria Delgado (The Netherlands), Paul Dendale (Belgium), Hans-Christoph Diener (Germany), Maria Dorobantu (Romania), Robert Fagard (Belgium), Csaba Farsang (Hungary), Marc Ferrini (France), Ian M. Graham (Ireland), Guido Grassi (Italy), Hermann Haller (Germany), F. D. Richard Hobbs (UK), Bojan Jelakovic (Croatia), Catriona Jennings (UK), Hugo A. Katus (Germany), Abraham A. Kroon (The Netherlands), Christophe Leclercq (France), Dragan Lovic (Serbia), Empar Lurbe (Spain), Athanasios J. Manolis (Greece), Theresa A. McDonagh (UK), Franz Messerli (Switzerland), Maria Lorenza Muiesan (Italy), Uwe Nixdorff (Germany), Michael Hecht Olsen (Denmark), Gianfranco Parati (Italy), Joep Perk (Sweden), Massimo Francesco Piepoli (Italy), Jorge Polonia (Portugal), Piotr Ponikowski (Poland), Dimitrios J. Richter (Greece), Stefano F. Rimoldi (Switzerland), Marco Roffi (Switzerland), Naveed Sattar (UK), Petar M. Seferovic (Serbia), Iain A. Simpson (UK), Miguel Sousa-Uva (Portugal), Alice V. Stanton (Ireland), Philippe van de Borne (Belgium), Panos Vardas (Greece), Massimo Volpe (Italy), Sven Wassmann (Germany), Stephan Windecker (Switzerland), Jose Luis Zamorano (Spain).The disclosure forms of all experts involved in the development of these Guidelines are available on the ESC website www.escardio.org/guidelines.
    Language English
    Publishing date 2018-09-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 605532-1
    ISSN 1473-5598 ; 0263-6352 ; 0952-1178
    ISSN (online) 1473-5598
    ISSN 0263-6352 ; 0952-1178
    DOI 10.1097/HJH.0000000000001940
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: 2018 Practice Guidelines for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension.

    Williams, Bryan / Mancia, Giuseppe / Spiering, Wilko / Agabiti Rosei, Enrico / Azizi, Michel / Burnier, Michel / Clement, Denis / Coca, Antonio / De Simone, Giovanni / Dominiczak, Anna / Kahan, Thomas / Mahfoud, Felix / Redon, Josep / Ruilope, Luis / Zanchetti, Alberto / Kerins, Mary / Kjeldsen, Sverre / Kreutz, Reinhold / Laurent, Stéphane /
    Lip, Gregory Y H / McManus, Richard / Narkiewicz, Krzysztof / Ruschitzka, Frank / Schmieder, Roland / Shlyakhto, Evgeny / Tsioufis, Konstantinos / Aboyans, Victor / Desormais, Ileana

    Blood pressure

    2018  Volume 27, Issue 6, Page(s) 314–340

    Abstract: These practice guidelines on the management of arterial hypertension are a concise summary of the more extensive ones prepared by the Task Force jointly appointed by the European Society of Hypertension and the European Society of Cardiology. These ... ...

    Abstract These practice guidelines on the management of arterial hypertension are a concise summary of the more extensive ones prepared by the Task Force jointly appointed by the European Society of Hypertension and the European Society of Cardiology. These guidelines have been prepared on the basis of the best available evidence on all issues deserving recommendations; their role must be educational and not prescriptive or coercive for the management of individual subjects who may differ widely in their personal, medical and cultural characteristics. The members of the Task Force have participated independently in the preparation of these guidelines, drawing on their academic and clinical experience and by objective examination and interpretation of all available literature. A disclosure of their potential conflict of interest is reported on the websites of the ESH and the ESC.
    MeSH term(s) Advisory Committees ; Europe ; Female ; Humans ; Hypertension/diagnosis ; Hypertension/epidemiology ; Hypertension/physiopathology ; Hypertension/therapy ; Male ; Societies, Medical
    Language English
    Publishing date 2018-10-31
    Publishing country England
    Document type Journal Article ; Practice Guideline ; Review
    ZDB-ID 1170048-8
    ISSN 1651-1999 ; 1651-2480 ; 0803-7051 ; 0803-8023
    ISSN (online) 1651-1999 ; 1651-2480
    ISSN 0803-7051 ; 0803-8023
    DOI 10.1080/08037051.2018.1527177
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: 2018 Practice Guidelines for the management of arterial hypertension of the European Society of Hypertension and the European Society of Cardiology: ESH/ESC Task Force for the Management of Arterial Hypertension.

    Williams, Bryan / Mancia, Giuseppe / Spiering, Wilko / Agabiti Rosei, Enrico / Azizi, Michel / Burnier, Michel / Clement, Denis / Coca, Antonio / De Simone, Giovanni / Dominiczak, Anna / Kahan, Thomas / Mahfoud, Felix / Redon, Josep / Ruilope, Luis / Zanchetti, Alberto / Kerins, Mary / Kjeldsen, Sverre / Kreutz, Reinhold / Laurent, Stephane /
    Lip, Gregory Y H / McManus, Richard / Narkiewicz, Krzysztof / Ruschitzka, Frank / Schmieder, Roland / Shlyakhto, Evgeny / Tsioufis, Konstantinos / Aboyans, Victor / Desormais, Ileana

    Journal of hypertension

    2018  Volume 36, Issue 12, Page(s) 2284–2309

    Language English
    Publishing date 2018-10-31
    Publishing country England
    Document type Journal Article
    ZDB-ID 605532-1
    ISSN 1473-5598 ; 0263-6352 ; 0952-1178
    ISSN (online) 1473-5598
    ISSN 0263-6352 ; 0952-1178
    DOI 10.1097/HJH.0000000000001961
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Coeficiente de caminhamento entre caracteres vegetativos e de produção de palmito da palmeira real australiana Path coefficient analysis between vegetative and heart-of-palm yield traits in Australian King palm

    Roberta Pierry Uzzo / Marilene L.A. Bovi / Sandra Heiden Spiering / Luís Alberto Sáes

    Horticultura Brasileira, Vol 22, Iss 1, Pp 136-

    2004  Volume 142

    Abstract: ... old) plants cultivated in an experiment carried out at Pariquera-Açu, São Paulo State, Brazil, were ...

    Abstract A determinação do coeficiente de caminhamento é bastante útil no melhoramento genético de plantas perenes. No presente estudo foram estimados os efeitos diretos e indiretos de cinco caracteres vegetativos da planta, relacionados ao crescimento, sobre os principais componentes da produção de palmito da palmeira real australiana (Archontophoenix alexandrae Wendl. & Drude), por meio do coeficiente de caminhamento. Para tanto, foram utilizados dados obtidos por ocasião da colheita realizada em 238 plantas de um experimento, com três de anos de campo, conduzido em Pariquera-Açu, SP. Desdobraram-se as correlações lineares simples existentes entre as variáveis padronizadas (dependentes e independentes), estabelecendo-se posteriormente um diagrama causal e identificando-se as inter-relações entre as variáveis envolvidas. Concluiu-se que o comprimento da folha flecha apresentou efeitos diretos e indiretos negativos e de baixa magnitude, evidenciando pouca influência na seleção de genótipos superiores, mas permitindo estabelecer, na prática, ponto adequado de colheita para maior retorno econômico. A maior magnitude dos coeficientes foi encontrada para a altura da planta, com efeitos diretos e indiretos elevados, positivos e significativos, explicando 85% da produção total. O diâmetro da planta, o número de folhas e o comprimento da quarta folha apresentaram efeitos diretos de baixa magnitude, porém positivos, podendo ser levados em consideração quando do estabelecimento de índices de seleção. Path coefficient is a useful technique in perennial plant breeding. Direct and indirect effects of five growth related vegetative traits, over the main heart-of-palm yield components from King palm (Archontophoenix alexandrae Wendl. & Drude) were estimated by path analysis. Harvesting data from 238 (three-year old) plants cultivated in an experiment carried out at Pariquera-Açu, São Paulo State, Brazil, were utilized. A casual diagram was established, and linear and simple standardized correlations were estimated in order to identify the interrelations between dependent and independent variables. Spear length showed small and negative direct and indirect effects, with low contribution to superior genotypes selection, although of practical importance to determine adequate harvesting timing for maximal economical value in this palm. The highest magnitude was found for plant height, with positive and significant direct and indirect effects, explaining 85% of the total yield. Plant diameter, leaf number and leaf size presented direct effects of low magnitude, although positive, should be considered only for selection indices establishment.
    Keywords Archontophoenix alexandrae ; caracteres agronômicos ; coeficiente de trilha ; melhoramento genético ; agronomic characters ; genetic improvement ; path coefficient ; Plant culture ; SB1-1110 ; Agriculture ; S ; DOAJ:Plant Sciences ; DOAJ:Agriculture and Food Sciences
    Language English
    Publishing date 2004-03-01T00:00:00Z
    Publisher Associação Brasileira de Olericultura
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Seasonal growth variation of peach palms cultivated in containers under subtropical conditions Variação estacional do crescimento em pupunheiras cultivadas em recipientes em condição subtropical

    Maria Luiza Sant'Anna Tucci / Marilene Leão Alves Bovi / Eduardo Caruso Machado / Sandra Heiden Spiering

    Scientia Agricola, Vol 64, Iss 2, Pp 138-

    2007  Volume 146

    Abstract: ... temperatura e precipitação pluviométrica, com possíveis efeitos na fisiologia das plantas. Recentemente ...

    Abstract Peach palm (Bactris gasipaes Kunth) is grown in the São Paulo State, Brazil, under climate seasonal variation conditions, mainly temperature and rainfal with possible effects on plant physiology. Recently, due to a higher interest in carrying out physiological experiments on the species, there has been a requirement for more controlled experimental conditions. Therefore, with the aim of studying the seasonal variation of peach palm growth for heart-of-palm production, as well as the possibility of growing them until harvest in pots, for future utilization in physiological experiments, this work was carried out in Campinas, SP, Brazil, with 40 spineless peach palms. One year after seed germination, seedlings were transplanted to 80 L plastic pots, spaced 2 x 1 m, arranged in four rows of ten plants. All plants had vegetative growth evaluated monthly by measurements of main stem height, number of functional leaves, number of offshoots and length of leaf raquis. Seasonal variations were observed in terms of height and diameter growth as well as raquis length of the youngest leaf and in the evolution of the number of leaves. After two years, plants had an average height of 230 cm, six functional leaves and 11.7 offshoots. Positive correlations (P < 0.001) were observed between growth variables and the average temperatures, rainfall as well as insolation of the 30, 60, 90 or 120 days previous to the measurements. Peach palms could be grown in containers until first harvest, without restrictions to growth. A pupunheira (Bactris gasipaes Kunth) é cultivada no Estado de São Paulo, Brasil, sob condições de variação estacional do clima, particularmente temperatura e precipitação pluviométrica, com possíveis efeitos na fisiologia das plantas. Recentemente, devido ao crescente interesse em se realizar experimentos sobre a fisiologia da espécie, tem havido necessidade de cultivá-la sob condições experimentais mais controladas. Com o objetivo de estudar a variação estacional do crescimento de pupunheiras, bem como a ...
    Keywords Bactris gasipaes ; palmito ; análise de crescimento ; heart of palm ; growth analysis ; Agriculture (General) ; S1-972
    Language English
    Publishing date 2007-01-01T00:00:00Z
    Publisher Universidade de São Paulo
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: 52 Genetic Loci Influencing Myocardial Mass.

    van der Harst, Pim / van Setten, Jessica / Verweij, Niek / Vogler, Georg / Franke, Lude / Maurano, Matthew T / Wang, Xinchen / Mateo Leach, Irene / Eijgelsheim, Mark / Sotoodehnia, Nona / Hayward, Caroline / Sorice, Rossella / Meirelles, Osorio / Lyytikäinen, Leo-Pekka / Polašek, Ozren / Tanaka, Toshiko / Arking, Dan E / Ulivi, Sheila / Trompet, Stella /
    Müller-Nurasyid, Martina / Smith, Albert V / Dörr, Marcus / Kerr, Kathleen F / Magnani, Jared W / Del Greco M, Fabiola / Zhang, Weihua / Nolte, Ilja M / Silva, Claudia T / Padmanabhan, Sandosh / Tragante, Vinicius / Esko, Tõnu / Abecasis, Gonçalo R / Adriaens, Michiel E / Andersen, Karl / Barnett, Phil / Bis, Joshua C / Bodmer, Rolf / Buckley, Brendan M / Campbell, Harry / Cannon, Megan V / Chakravarti, Aravinda / Chen, Lin Y / Delitala, Alessandro / Devereux, Richard B / Doevendans, Pieter A / Dominiczak, Anna F / Ferrucci, Luigi / Ford, Ian / Gieger, Christian / Harris, Tamara B / Haugen, Eric / Heinig, Matthias / Hernandez, Dena G / Hillege, Hans L / Hirschhorn, Joel N / Hofman, Albert / Hubner, Norbert / Hwang, Shih-Jen / Iorio, Annamaria / Kähönen, Mika / Kellis, Manolis / Kolcic, Ivana / Kooner, Ishminder K / Kooner, Jaspal S / Kors, Jan A / Lakatta, Edward G / Lage, Kasper / Launer, Lenore J / Levy, Daniel / Lundby, Alicia / Macfarlane, Peter W / May, Dalit / Meitinger, Thomas / Metspalu, Andres / Nappo, Stefania / Naitza, Silvia / Neph, Shane / Nord, Alex S / Nutile, Teresa / Okin, Peter M / Olsen, Jesper V / Oostra, Ben A / Penninger, Josef M / Pennacchio, Len A / Pers, Tune H / Perz, Siegfried / Peters, Annette / Pinto, Yigal M / Pfeufer, Arne / Pilia, Maria Grazia / Pramstaller, Peter P / Prins, Bram P / Raitakari, Olli T / Raychaudhuri, Soumya / Rice, Ken M / Rossin, Elizabeth J / Rotter, Jerome I / Schafer, Sebastian / Schlessinger, David / Schmidt, Carsten O / Sehmi, Jobanpreet / Silljé, Herman H W / Sinagra, Gianfranco / Sinner, Moritz F / Slowikowski, Kamil / Soliman, Elsayed Z / Spector, Timothy D / Spiering, Wilko / Stamatoyannopoulos, John A / Stolk, Ronald P / Strauch, Konstantin / Tan, Sian-Tsung / Tarasov, Kirill V / Trinh, Bosco / Uitterlinden, Andre G / van den Boogaard, Malou / van Duijn, Cornelia M / van Gilst, Wiek H / Viikari, Jorma S / Visscher, Peter M / Vitart, Veronique / Völker, Uwe / Waldenberger, Melanie / Weichenberger, Christian X / Westra, Harm-Jan / Wijmenga, Cisca / Wolffenbuttel, Bruce H / Yang, Jian / Bezzina, Connie R / Munroe, Patricia B / Snieder, Harold / Wright, Alan F / Rudan, Igor / Boyer, Laurie A / Asselbergs, Folkert W / van Veldhuisen, Dirk J / Stricker, Bruno H / Psaty, Bruce M / Ciullo, Marina / Sanna, Serena / Lehtimäki, Terho / Wilson, James F / Bandinelli, Stefania / Alonso, Alvaro / Gasparini, Paolo / Jukema, J Wouter / Kääb, Stefan / Gudnason, Vilmundur / Felix, Stephan B / Heckbert, Susan R / de Boer, Rudolf A / Newton-Cheh, Christopher / Hicks, Andrew A / Chambers, John C / Jamshidi, Yalda / Visel, Axel / Christoffels, Vincent M / Isaacs, Aaron / Samani, Nilesh J / de Bakker, Paul I W

    Journal of the American College of Cardiology

    2016  Volume 68, Issue 13, Page(s) 1435–1448

    Abstract: Background: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). ... ...

    Abstract Background: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death.
    Objectives: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass.
    Methods: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment.
    Results: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo.
    Conclusions: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets.
    MeSH term(s) Animals ; Cardiomegaly/genetics ; Genetic Loci ; Genome-Wide Association Study ; Humans
    Language English
    Publishing date 2016-09-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 605507-2
    ISSN 1558-3597 ; 0735-1097
    ISSN (online) 1558-3597
    ISSN 0735-1097
    DOI 10.1016/j.jacc.2016.07.729
    Database MEDical Literature Analysis and Retrieval System OnLINE

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