دورية أكاديمية
Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease.
| العنوان: | Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease. |
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| المؤلفون: | Zanoni, P., Khetarpal, S.A., Larach, D.B., Hancock-Cerutti, W.F., Millar, J.S., Cuchel, M., Derohannessian, S.L., Kontush, A., Surendran, P., Saleheen, D., Trompet, S., Jukema, J.W., de Craen, A.J., Deloukas, P., Sattar, N., Ford, I., Packard, C., Al Shafi Majumder, A., Alam, D.S., di Angelantonio, E., Abecasis, G., Chowdhury, R., Erdmann, J., Nørdestgaard, B.G., Nielsen, S.F., Tybjærg-Hansen, A., Schmidt, R.F., Kuulasmaa, K., Liu, D.J., Perola, M., Blankenberg, S., Salomaa, V., Männistö, S., Amouyel, P., Arveiler, D., Ferrieres, J., Müller-Nurasyid, M., Ferrario, M., Kee, F., Willer, C.J., Samani, N., Schunkert, H., Butterworth, A.S., Howson, J.M.M., Peloso, G.M., Stitziel, N.O., Danesh, J., Kathiresan, S., Rader, D.J., CHD Exome Consortium (), CARDIoGRAM Exome Consortium (), Global Lipids Genetics Consortium () |
| المصدر: | Science 351, 1166-1671 (2016) |
| بيانات النشر: | Amer Assoc Advancement Science |
| سنة النشر: | 2016 |
| المجموعة: | PuSH - Publikationsserver des Helmholtz Zentrums München |
| 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. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant). |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0036-8075 1095-9203 |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/26965621; info:eu-repo/semantics/altIdentifier/wos/WOS:000386158400038; info:eu-repo/semantics/altIdentifier/isbn/0036-8075; info:eu-repo/semantics/al; https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=48090Test; urn:isbn:0036-8075; urn:issn:0036-8075; urn:issn:1095-9203 |
| DOI: | 10.1126/science.aad3517 |
| الإتاحة: | https://doi.org/10.1126/science.aad3517Test https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=48090Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.1A5B0355 |
| قاعدة البيانات: | BASE |
| تدمد: | 00368075 10959203 |
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| DOI: | 10.1126/science.aad3517 |