التفاصيل البيبلوغرافية
| العنوان: |
Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease Item Type Article Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease |
| المؤلفون: |
P, Zanoni, S A, Khetarpal, D B, Larach, W F, Hancock-Cerutti, Paolo Zanoni, Sumeet A Khetarpal, Daniel B Larach, William F Hancock-Cerutti, John S Millar, Marina Cuchel, Stephanie Derohannessian, Anatol Kontush, Praveen Surendran, Danish Saleheen, Stella Trompet, J Wouter Jukema, Anton De Craen, Panos Deloukas, Naveed Sattar, Ian Ford, Chris Packard, Abdullah Al, Shafi Majumder, Dewan S Alam, Emanuele Di Angelantonio, Goncalo Abecasis, Rajiv Chowdhury, Jeanette Erdmann, Børge G Nordestgaard, Sune F Nielsen, Anne Tybjaerg-Hansen, Ruth Frikke Schmidt, Kari Kuulasmaa, Dajiang J Liu, Markus Perola, Stefan Blankenberg, Veikko Salomaa, Satu Männistö, Philippe Amouyel, Dominique Arveiler, Jean Ferrieres, Martina Müller-Nurasyid, Marco Ferrario, Frank Kee, Cristen J Willer, Nilesh Samani, Heribert Schunkert, Adam S Butterworth, Joanna M M Howson, Gina M Peloso, Nathan O Stitziel, John Danesh, Sekar Kathiresan, Daniel J Rader |
| المساهمون: |
The Pennsylvania State University CiteSeerX Archives |
| المصدر: |
http://arizona.openrepository.com/arizona/bitstream/10150/623258/3/Rare%2Bvariant%2Bin%2Bscavenger%2Breceptor%2BBI%2Braises%2BHDL%2Bcholesterol%2Band%2Bincreases%2Brisk%2Bof%2Bcoronary%2Bheart%2Bdisease.pdfTest. |
| المجموعة: |
CiteSeerX |
| الوصف: |
Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. Zanoni et al. Page 2 P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant). The strong inverse association between amounts of high-density lipoprotein (HDL) cholesterol (HDL-C) and coronary heart disease (CHD) risk has generated interest in a potential causal relationship between HDL metabolism and CHD. However, clinical trials with drugs that raise HDL-C levels, niacin and cholesteryl ester transfer protein (CETP) inhibitors, have produced disappointing results ( 1 ). Furthermore, recent studies of human genetic variants that are associated with HDL-C levels have generally failed to show association with CHD ( 2 , 3 ). Most notably, a loss-of-function variant in LIPG, a gene encoding an endothelial lipase that, in the heterozygous state, raises HDL-C by ~5 mg/dl, was found to have no association with CHD ( 4 ). Although these previous ... |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.1051.7174Test; http://arizona.openrepository.com/arizona/bitstream/10150/623258/3/Rare%2Bvariant%2Bin%2Bscavenger%2Breceptor%2BBI%2Braises%2BHDL%2Bcholesterol%2Band%2Bincreases%2Brisk%2Bof%2Bcoronary%2Bheart%2Bdisease.pdfTest |
| الإتاحة: |
http://arizona.openrepository.com/arizona/bitstream/10150/623258/3/Rare%2Bvariant%2Bin%2Bscavenger%2Breceptor%2BBI%2Braises%2BHDL%2Bcholesterol%2Band%2Bincreases%2Brisk%2Bof%2Bcoronary%2Bheart%2Bdisease.pdfTest |
| حقوق: |
Metadata may be used without restrictions as long as the oai identifier remains attached to it. |
| رقم الانضمام: |
edsbas.1377E9D |
| قاعدة البيانات: |
BASE |
