Forty-Three Loci Associated with Plasma Lipoprotein Size, Concentration, and Cholesterol Content in Genome-Wide Analysis

被引：266

作者：

Chasman, Daniel I. ^{[1
,2
]}

Pare, Guillaume ^{[1
,2
]}

Mora, Samia ^{[1
,2
,3
]}

Hopewell, Jemma C. ^{[4
,5
]}

Peloso, Gina ^{[6
]}

Clarke, Robert ^{[4
,5
]}

Cupples, L. Adrienne ^{[6
,7
]}

Hamsten, Anders ^{[4
,8
]}

Kathiresan, Sekar ^{[9
,10
]}

Maelarstig, Anders ^{[4
,8
]}

Ordovas, Jose M. ^{[11
]}

Ripatti, Samuli ^{[12
]}

Parker, Alex N. ^{[13
]}

Miletich, Joseph P. ^{[14
]}

Ridker, Paul M. ^{[1
,2
,3
]}

机构：

[1] Brigham & Womens Hosp, Donald W Reynolds Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA

[4] Univ Oxford, PROCARDIS Consortium, Oxford, England

[5] Univ Oxford, Clin Trial Serv Unit, Oxford, England

[6] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[7] Boston Univ, Sch Med, Framingham Heart Study, Boston, MA 02118 USA

[8] Karolinska Inst, Dept Med, Atherosclerosis Res Unit, Stockholm, Sweden

[9] MIT, Broad Inst, Cambridge, MA 02139 USA

[10] Harvard Univ, Cambridge, MA 02138 USA

[11] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA

[12] FIMM, Inst Mol Med Finland, Helsinki, Finland

[13] Amgen Inc, Cambridge, MA USA

[14] Amgen Inc, Thousand Oaks, CA 91320 USA

来源：

PLOS GENETICS | 2009年 / 5卷 / 11期

基金：

英国医学研究理事会;

关键词：

CORONARY-ARTERY-DISEASE; MAGNETIC-RESONANCE-SPECTROSCOPY; SPLICE-SITE MUTATION; C-REACTIVE PROTEIN; MYOCARDIAL-INFARCTION; METABOLIC-SYNDROME; SERUM-CHOLESTEROL; BLOOD-GROUPS; RISK; POPULATION;

D O I：

10.1371/journal.pgen.1000730

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

While conventional LDL-C, HDL-C, and triglyceride measurements reflect aggregate properties of plasma lipoprotein fractions, NMR-based measurements more accurately reflect lipoprotein particle concentrations according to class (LDL, HDL, and VLDL) and particle size (small, medium, and large). The concentrations of these lipoprotein sub-fractions may be related to risk of cardiovascular disease and related metabolic disorders. We performed a genome-wide association study of 17 lipoprotein measures determined by NMR together with LDL-C, HDL-C, triglycerides, ApoA1, and ApoB in 17,296 women from the Women's Genome Health Study (WGHS). Among 36 loci with genome-wide significance (P<5 x 10(-8)) in primary and secondary analysis, ten (PCCB/STAG1 (3q22.3), GMPR/MYLIP (6p22.3), BTNL2 (6p21.32), KLF14 (7q32.2), 8p23.1, JMJD1C (10q21.3), SBF2 (11p15.4), 12q23.2, CCDC92/DNAH10/ZNF664 (12q24.31.B), and WIPI1 (17q24.2)) have not been reported in prior genome-wide association studies for plasma lipid concentration. Associations with mean lipoprotein particle size but not cholesterol content were found for LDL at four loci (7q11.23, LPL (8p21.3), 12q24.31.B, and LIPG (18q21.1)) and for HDL at one locus (GCKR (2p23.3)). In addition, genetic determinants of total IDL and total VLDL concentration were found at many loci, most strongly at LIPC (15q22.1) and APOC-APOE complex (19q13.32), respectively. Associations at seven more loci previously known for effects on conventional plasma lipid measures reveal additional genetic influences on lipoprotein profiles and bring the total number of loci to 43. Thus, genome-wide associations identified novel loci involved with lipoprotein metabolism-including loci that affect the NMR-based measures of concentration or size of LDL, HDL, and VLDL particles-all characteristics of lipoprotein profiles that may impact disease risk but are not available by conventional assay.

引用

页数：14

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