Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease
Authors: Zanoni Paolo , Khetarpal Sumeet A. , Larach Daniel B. , Hancock-Cerutti William F. , Millar John S. , Cuchel Marina , DerOhannessian Stephanie , Kontush Anatol , Surendran Praveen , Saleheen Danish , Trompet Stella , Jukema J. Wouter , De Craen Anton , Deloukas Panos , Sattar Naveed , Ford Ian , Packard Chris , Majumder Abdullah al Shafi , Alam Dewan S. , Di Angelantonio Emanuele , Abecasis Goncalo , Chowdhury Rajiv , Erdmann Jeanette , Nordestgaard Børge G. , Nielsen Sune F. , Tybjærg-Hansen Anne , Schmidt Ruth Frikke , Kuulasmaa Kari , Liu Dajiang J. , Perola Markus , Blankenberg Stefan , Salomaa Veikko , Männistö Satu , Amouyel Philippe , Arveiler Dominique , Ferrieres Jean , Müller-Nurasyid Martina , Ferrario Marco , Kee Frank , Willer Cristen J. , Samani Nilesh , Schunkert Heribert , Butterworth Adam S. , Howson Joanna M. M. , Peloso Gina M. , Stitziel Nathan O. , Danesh John , Kathiresan Sekar , Rader Daniel J. ,   CHD Exome+ Consortium,   CARDIoGRAM Exome Consortium,   Global Lipids Genetics Consortium, Watson Sarah , Schmidt Ellen M. , Sengupta Sebanti , Gustafsson Stefan , Kanoni Stavroula , Ganna Andrea , Chen Jin , Buchkovich Martin L. , Mora Samia , Beckmann Jacques S. , Bragg-Gresham Jennifer L. , Chang Hsing-Yi , Demirkan Ayşe , Den Hertog Heleen M. , Do Ron , Donnelly Louise A. , Ehret Georg B. , Esko Tõnu , Feitosa Mary F. , Ferreira Teresa , Fischer Krista , Fontanillas Pierre , Fraser Ross M. , Freitag Daniel F. , Gurdasani Deepti , Heikkilä Kauko , Hyppönen Elina , Isaacs Aaron , Jackson Anne U. , Johansson Åsa , Johnson Toby , Kaakinen Marika , Kettunen Johannes , Kleber Marcus E. , Li Xiaohui , Luan Jian’an , Lyytikäinen Leo-Pekka , Magnusson Patrik K. E. , Mangino Massimo , Mihailov Evelin , Montasser May E. , Nolte Ilja M. , O’Connell Jeffrey R. , Palmer Cameron D. , Petersen Ann-Kristin , Sanna Serena , Saxena Richa , Service Susan K. , Shah Sonia , Shungin Dmitry , Sidore Carlo , Song Ci , Strawbridge Rona J. , Surakka Ida , Tanaka Toshiko , Teslovich Tanya M. , Thorleifsson Gudmar , Van den Herik Evita G. , Voight Benjamin F. , Volcik Kelly A. , Waite Lindsay L. , Wong Andrew , Wu Ying , Zhang Weihua , Absher Devin , Asiki Gershim , Barroso Inês , Been Latonya F. , Bolton Jennifer L. , Bonnycastle Lori L. , Brambilla Paolo , Burnett Mary S. , Cesana Giancarlo , Dimitriou Maria , Doney Alex S. F. , Döring Angela , Elliott Paul , Epstein Stephen E. , Eyjolfsson Gudmundur Ingi , Gigante Bruna , Goodarzi Mark O. , Grallert Harald , Gravito Martha L. , Groves Christopher J. , Hallmans Göran , Hartikainen Anna-Liisa , Hayward Caroline , Hernandez Dena , Hicks Andrew A. , Holm Hilma , Hung Yi-Jen , Illig Thomas , Jones Michelle R. , Kaleebu Pontiano , Kastelein John J. P. , Khaw Kay-Tee , Kim Eric , Klopp Norman , Komulainen Pirjo , Kumari Meena , Langenberg Claudia , Lehtimäki Terho , Lin Shih-Yi , Lindström Jaana , Loos Ruth J. F. , Mach François , McArdle Wendy L. , Meisinger Christa , Mitchell Braxton D. , Müller Gabrielle , Nagaraja Ramaiah , Narisu Narisu , Nieminen Tuomo V. M. , Nsubuga Rebecca N. , Olafsson Isleifur , Ong Ken K. , Palotie Aarno , Papamarkou Theodore , Pomilla Cristina , Pouta Anneli , Reilly Muredach P. , Ridker Paul M. , Rivadeneira Fernando , Rudan Igor , Ruokonen Aimo , Scharnagl Hubert , Seeley Janet , Silander Kaisa , Stancáková Alena , Stirrups Kathleen , Swift Amy J. , Tiret Laurence , Uitterlinden Andre G. , van Pelt L. J. , Vedantam Sailaja , Wainwright Nicholas , Wijmenga Cisca , Wild Sarah H. , Willemsen Gonneke , Wilsgaard Tom , Wilson James F. , Young Elizabeth H. , Zhao Jing Hua , Adair Linda S. , Arveiler Dominique , Assimes Themistocles L. , Bandinelli Stefania , Bennett Franklyn , Bochud Murielle , Boehm Bernhard O. , Boomsma Dorret I. , Borecki Ingrid B. , Bornstein Stefan R. , Bovet Pascal , Burnier Michel , Campbell Harry , Chakravarti Aravinda , Chambers John C. , Chen Yii-Der Ida , Collins Francis S. , Cooper Richard S. , Dedoussis George , de Faire Ulf , Feranil Alan B. , Ferrucci Luigi , Freimer Nelson B. , Gieger Christian , Groop Leif C. , Gudnason Vilmundur , Gyllensten Ulf , Hamsten Anders , Harris Tamara B. , Hingorani Aroon , Hirschhorn Joel N. , Hofman Albert , Hovingh G. Kees , Hsiung Chao Agnes , Humphries Steve E. , Hunt Steven C. , Hveem Kristian , Iribarren Carlos , Järvelin Marjo-Riitta , Jula Antti , Kähönen Mika , Kaprio Jaakko , Kesäniemi Antero , Kivimaki Mika , Kooner Jaspal S. , Koudstaal Peter J. , Krauss Ronald M. , Kuh Diana , Kuusisto Johanna , Kyvik Kirsten O. , Laakso Markku , Lakka Timo A. , Lind Lars , Lindgren Cecilia M. , Martin Nicholas G. , März Winfried , McCarthy Mark I. , McKenzie Colin A. , Meneton Pierre , Metspalu Andres , Moilanen Leena , Morris Andrew D. , Munroe Patricia B. , Njølstad Inger , Pedersen Nancy L. , Power Chris , Pramstaller Peter P. , Price Jackie F. , Psaty Bruce M. , Quertermous Thomas , Rauramaa Rainer , Salomaa Veikko , Sanghera Dharambir K. , Saramies Jouko , Schwarz Peter E. H. , Sheu Wayne H.-H. , Shuldiner Alan R. , Siegbahn Agneta , Spector Tim D. , Stefansson Kari , Strachan David P. , Tayo Bamidele O. , Tremoli Elena , Tuomilehto Jaakko , Uusitupa Matti , van Duijn Cornelia M. , Vollenweider Peter , Wallentin Lars , Wareham Nicholas J. , Whitfield John B. , Wolffenbuttel Bruce H. R. , Ordovas Jose M. , Boerwinkle Eric , Palmer Colin N. A. , Thorsteinsdottir Unnur , Chasman Daniel I. , Rotter Jerome I. , Franks Paul W. , Riatti Samuli , Cupples L. Adrienne , Sandhu Manjinder S. , Rich Stephen S. , Boehnke Michael , Deloukas Panos , Mohlke Karen L. , Ingelsson Erik , Gu Dongfeng , Roberts Robert , Watkins Hugh , Blankenberg Stefan , Clarke Robert , Collins Rory , Kim Bong-Jo , McPherson Ruth , Nieminen Markku S. , O'Donnell Christopher , Schreiber Stefan , Siegbahn Agneta , Zalloua Pierre A. 
Published: March 2016

A scavenger that protects the heart

Coronary heart disease is a tale of two forms of plasma cholesterol. In contrast to the well-established effects of “bad” cholesterol (LDL-C), the role of “good” cholesterol (HDL-C) is mysterious. Elevated HDL-C correlates with a lower risk of heart disease, yet drugs that raise HDL-C levels do not reduce risk. Zanoni
et al.
found that some people with exceptionally high levels of HDL-C carry a rare sequence variant in the gene encoding the major HDL-C receptor, scavenger receptor BI. This variant destroys the receptor's ability to take up HDL-C. Interestingly, people with this variant have a higher risk of heart disease despite having high levels of HDL-C.

Science
, this issue p.
1166