Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease
Zanoni P., Khetarpal SA., Larach DB., Hancock-Cerutti WF., Millar JS., Cuchel M., DerOhannessian S., Kontush A., Surendran P., Saleheen D., Trompet S., Jukema JW., De Craen A., Deloukas P., Sattar N., Ford I., Packard C., Majumder AAS., Alam DS., Di Angelantonio E., Abecasis G., Chowdhury R., Erdmann J., Nordestgaard BG., Nielsen SF., Tybjærg-Hansen A., Schmidt RF., Kuulasmaa K., Liu DJ., Perola M., Blankenberg S., Salomaa V., Männistö S., Amouyel P., Arveiler D., Ferrieres J., Müller-Nurasyid M., Ferrario M., Kee F., Willer CJ., Samani N., Schunkert H., Butterworth AS., Howson JMM., Peloso GM., Stitziel NO., Danesh J., Kathiresan S., Rader DJ., Watson S., Schmidt EM., Sengupta S., Gustafsson S., Kanoni S., Ganna A., Chen J., Buchkovich ML., Mora S., Beckmann JS., Bragg-Gresham JL., Chang H-Y., Demirkan A., Den Hertog HM., Do R., Donnelly LA., Ehret GB., Esko T., Feitosa MF., Ferreira T., Fischer K., Fontanillas P., Fraser RM., Freitag DF., Gurdasani D., Heikkilä K., Hyppönen E., Isaacs A., Jackson AU., Johansson Å., Johnson T., Kaakinen M., Kettunen J., Kleber ME., Li X., Luan J., Lyytikäinen L-P., Magnusson PKE., Mangino M., Mihailov E., Montasser ME., Nolte IM., O’Connell JR., Palmer CD., Petersen A-K., Sanna S., Saxena R., Service SK., Shah S., Shungin D., Sidore C., Song C., Strawbridge RJ., Surakka I., Tanaka T., Teslovich TM., Thorleifsson G., Van den Herik EG., Voight BF., Volcik KA., Waite LL., Wong A., Wu Y., Zhang W., Absher D., Asiki G., Barroso I., Been LF., Bolton JL., Bonnycastle LL., Brambilla P., Burnett MS., Cesana G., Dimitriou M., Doney ASF., Döring A., Elliott P., Epstein SE., Eyjolfsson GI., Gigante B., Goodarzi MO., Grallert H., Gravito ML., Groves CJ., Hallmans G., Hartikainen A-L., Hayward C., Hernandez D., Hicks AA., Holm H., Hung Y-J., Illig T., Jones MR., Kaleebu P., Kastelein JJP., Khaw K-T., Kim E., Klopp N., Komulainen P., Kumari M., Langenberg C., Lehtimäki T., Lin S-Y., Lindström J., Loos RJF., Mach F., McArdle WL., Meisinger C., Mitchell BD., Müller G., Nagaraja R., Narisu N., Nieminen TVM., Nsubuga RN., Olafsson I., Ong KK., Palotie A., Papamarkou T., Pomilla C., Pouta A., Reilly MP., Ridker PM., Rivadeneira F., Rudan I., Ruokonen A., Scharnagl H., Seeley J., Silander K., Stancáková A., Stirrups K., Swift AJ., Tiret L., Uitterlinden AG., van Pelt LJ., Vedantam S., Wainwright N., Wijmenga C., Wild SH., Willemsen G., Wilsgaard T., Wilson JF., Young EH., Zhao JH., Adair LS., Arveiler D., Assimes TL., Bandinelli S., Bennett F., Bochud M., Boehm BO., Boomsma DI., Borecki IB., Bornstein SR., Bovet P., Burnier M., Campbell H., Chakravarti A., Chambers JC., Chen Y-DI., Collins FS., Cooper RS., Dedoussis G., de Faire U., Feranil AB., Ferrucci L., Freimer NB., Gieger C., Groop LC., Gudnason V., Gyllensten U., Hamsten A., Harris TB., Hingorani A., Hirschhorn JN., Hofman A., Hovingh GK., Hsiung CA., Humphries SE., Hunt SC., Hveem K., Iribarren C., Järvelin M-R., Jula A., Kähönen M., Kaprio J., Kesäniemi A., Kivimaki M., Kooner JS., Koudstaal PJ., Krauss RM., Kuh D., Kuusisto J., Kyvik KO., Laakso M., Lakka TA., Lind L., Lindgren CM., Martin NG., März W., McCarthy MI., McKenzie CA., Meneton P., Metspalu A., Moilanen L., Morris AD., Munroe PB., Njølstad I., Pedersen NL., Power C., Pramstaller PP., Price JF., Psaty BM., Quertermous T., Rauramaa R., Salomaa V., Sanghera DK., Saramies J., Schwarz PEH., Sheu WH-H., Shuldiner AR., Siegbahn A., Spector TD., Stefansson K., Strachan DP., Tayo BO., Tremoli E., Tuomilehto J., Uusitupa M., van Duijn CM., Vollenweider P., Wallentin L., Wareham NJ., Whitfield JB., Wolffenbuttel BHR., Ordovas JM., Boerwinkle E., Palmer CNA., Thorsteinsdottir U., Chasman DI., Rotter JI., Franks PW., Riatti S., Cupples LA., Sandhu MS., Rich SS., Boehnke M., Deloukas P., Mohlke KL., Ingelsson E., Gu D., Roberts R., Watkins H., Blankenberg S., Clarke R., Collins R., Kim B-J., McPherson R., Nieminen MS., O'Donnell C., Schreiber S., Siegbahn A., Zalloua PA.
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