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Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans.

Standard

Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans. / Edmondson, Andrew C; Brown, Robert J; Kathiresan, Sekar; Cupples, L Adrienne; Demissie, Serkalem; Manning, Alisa Knodle; Jensen, Majken K; Rimm, Eric B; Wang, Jian; Rodrigues, Amrith; Bamba, Vaneeta; Khetarpal, Sumeet A; Wolfe, Megan L; Derohannessian, Stephanie; Li, Mingyao; Reilly, Muredach P; Aberle, Jens; Evans, David; Hegele, Robert A; Rader, Daniel J.

in: J CLIN INVEST, Jahrgang 119, Nr. 4, 4, 2009, S. 1042-1050.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Edmondson, AC, Brown, RJ, Kathiresan, S, Cupples, LA, Demissie, S, Manning, AK, Jensen, MK, Rimm, EB, Wang, J, Rodrigues, A, Bamba, V, Khetarpal, SA, Wolfe, ML, Derohannessian, S, Li, M, Reilly, MP, Aberle, J, Evans, D, Hegele, RA & Rader, DJ 2009, 'Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans.', J CLIN INVEST, Jg. 119, Nr. 4, 4, S. 1042-1050. <http://www.ncbi.nlm.nih.gov/pubmed/19287092?dopt=Citation>

APA

Edmondson, A. C., Brown, R. J., Kathiresan, S., Cupples, L. A., Demissie, S., Manning, A. K., Jensen, M. K., Rimm, E. B., Wang, J., Rodrigues, A., Bamba, V., Khetarpal, S. A., Wolfe, M. L., Derohannessian, S., Li, M., Reilly, M. P., Aberle, J., Evans, D., Hegele, R. A., & Rader, D. J. (2009). Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans. J CLIN INVEST, 119(4), 1042-1050. [4]. http://www.ncbi.nlm.nih.gov/pubmed/19287092?dopt=Citation

Vancouver

Edmondson AC, Brown RJ, Kathiresan S, Cupples LA, Demissie S, Manning AK et al. Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans. J CLIN INVEST. 2009;119(4):1042-1050. 4.

Bibtex

@article{c85acccdd8004678988b687db05d6e1a,
title = "Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans.",
abstract = "Elevated plasma concentrations of HDL cholesterol (HDL-C) are associated with protection from atherosclerotic cardiovascular disease. Animal models indicate that decreased expression of endothelial lipase (LIPG) is inversely associated with HDL-C levels, and genome-wide association studies have identified LIPG variants as being associated with HDL-C levels in humans. We hypothesized that loss-of-function mutations in LIPG may result in elevated HDL-C and therefore performed deep resequencing of LIPG exons in cases with elevated HDL-C levels and controls with decreased HDL-C levels. We identified a significant excess of nonsynonymous LIPG variants unique to cases with elevated HDL-C. In vitro lipase activity assays demonstrated that these variants significantly decreased endothelial lipase activity. In addition, a meta-analysis across 5 cohorts demonstrated that the low-frequency Asn396Ser variant is significantly associated with increased HDL-C, while the common Thr111Ile variant is not. Functional analysis confirmed that the Asn396Ser variant has significantly decreased lipase activity both in vitro and in vivo, while the Thr111Ile variant has normal lipase activity. Our results establish that loss-of-function mutations in LIPG lead to increased HDL-C levels and support the idea that inhibition of endothelial lipase may be an effective mechanism to raise HDL-C.",
author = "Edmondson, {Andrew C} and Brown, {Robert J} and Sekar Kathiresan and Cupples, {L Adrienne} and Serkalem Demissie and Manning, {Alisa Knodle} and Jensen, {Majken K} and Rimm, {Eric B} and Jian Wang and Amrith Rodrigues and Vaneeta Bamba and Khetarpal, {Sumeet A} and Wolfe, {Megan L} and Stephanie Derohannessian and Mingyao Li and Reilly, {Muredach P} and Jens Aberle and David Evans and Hegele, {Robert A} and Rader, {Daniel J}",
year = "2009",
language = "Deutsch",
volume = "119",
pages = "1042--1050",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "4",

}

RIS

TY - JOUR

T1 - Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans.

AU - Edmondson, Andrew C

AU - Brown, Robert J

AU - Kathiresan, Sekar

AU - Cupples, L Adrienne

AU - Demissie, Serkalem

AU - Manning, Alisa Knodle

AU - Jensen, Majken K

AU - Rimm, Eric B

AU - Wang, Jian

AU - Rodrigues, Amrith

AU - Bamba, Vaneeta

AU - Khetarpal, Sumeet A

AU - Wolfe, Megan L

AU - Derohannessian, Stephanie

AU - Li, Mingyao

AU - Reilly, Muredach P

AU - Aberle, Jens

AU - Evans, David

AU - Hegele, Robert A

AU - Rader, Daniel J

PY - 2009

Y1 - 2009

N2 - Elevated plasma concentrations of HDL cholesterol (HDL-C) are associated with protection from atherosclerotic cardiovascular disease. Animal models indicate that decreased expression of endothelial lipase (LIPG) is inversely associated with HDL-C levels, and genome-wide association studies have identified LIPG variants as being associated with HDL-C levels in humans. We hypothesized that loss-of-function mutations in LIPG may result in elevated HDL-C and therefore performed deep resequencing of LIPG exons in cases with elevated HDL-C levels and controls with decreased HDL-C levels. We identified a significant excess of nonsynonymous LIPG variants unique to cases with elevated HDL-C. In vitro lipase activity assays demonstrated that these variants significantly decreased endothelial lipase activity. In addition, a meta-analysis across 5 cohorts demonstrated that the low-frequency Asn396Ser variant is significantly associated with increased HDL-C, while the common Thr111Ile variant is not. Functional analysis confirmed that the Asn396Ser variant has significantly decreased lipase activity both in vitro and in vivo, while the Thr111Ile variant has normal lipase activity. Our results establish that loss-of-function mutations in LIPG lead to increased HDL-C levels and support the idea that inhibition of endothelial lipase may be an effective mechanism to raise HDL-C.

AB - Elevated plasma concentrations of HDL cholesterol (HDL-C) are associated with protection from atherosclerotic cardiovascular disease. Animal models indicate that decreased expression of endothelial lipase (LIPG) is inversely associated with HDL-C levels, and genome-wide association studies have identified LIPG variants as being associated with HDL-C levels in humans. We hypothesized that loss-of-function mutations in LIPG may result in elevated HDL-C and therefore performed deep resequencing of LIPG exons in cases with elevated HDL-C levels and controls with decreased HDL-C levels. We identified a significant excess of nonsynonymous LIPG variants unique to cases with elevated HDL-C. In vitro lipase activity assays demonstrated that these variants significantly decreased endothelial lipase activity. In addition, a meta-analysis across 5 cohorts demonstrated that the low-frequency Asn396Ser variant is significantly associated with increased HDL-C, while the common Thr111Ile variant is not. Functional analysis confirmed that the Asn396Ser variant has significantly decreased lipase activity both in vitro and in vivo, while the Thr111Ile variant has normal lipase activity. Our results establish that loss-of-function mutations in LIPG lead to increased HDL-C levels and support the idea that inhibition of endothelial lipase may be an effective mechanism to raise HDL-C.

M3 - SCORING: Zeitschriftenaufsatz

VL - 119

SP - 1042

EP - 1050

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 4

M1 - 4

ER -