Lp-PLA2, scavenger receptor class B type I gene (SCARB1) rs10846744 variant, and cardiovascular disease.
Lp-PLA2, scavenger receptor class B type I gene (SCARB1) rs10846744 variant, and cardiovascular disease.
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DOI：
10.1371/journal.pone.0204352
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Rodriguez A
中科院分区：
文献类型：
--
作者：
Manichaikul A;Wang XQ;Li L;Erdmann J;Lettre G;Bis JC;Waterworth D;Cushman M;Jenny NS;Post WS;Palmas W;Tsai MY;Wallentin L;White H;Schunkert H;O'Donnell CJ;Herrington DM;Rich SS;O'Donoghue ML;Rodriguez A
We previously reported association of SCARB1 SNP rs10846744 with common carotid IMT (cIMT) and cardiovascular disease (CVD) events. Since rs10846744 has been reported in association with Lp-PLA2 mass and activity, we hypothesized that inflammatory pathways might mediate the association of rs10846744 with atherosclerosis. We first examined association of rs10846744 in CVD in multiple large-scale consortium-based genome-wide association studies. We further examined 27 parameters of interest, including Lp-PLA2 mass and activity, inflammatory markers, and plasma phospholipid fatty acids, and fatty acid ratios in participants from the Multi-Ethnic Study of Atherosclerosis (MESA), as potential mediators in the pathway linking rs10846744 with cIMT and incident CVD. Finally, we examined the association of rs10846744 with Lp-PLA2 activity, cardiovascular outcomes, and interaction with the Lp-PLA2 inhibitor, darapladib, in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) and Stabilization of Plaque using Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID-TIMI 52) studies. SCARB1 rs10846744 was associated with coronary artery disease events in CARDIoGRAMplusC4D (odds ratio 1.05; 95% CI [1.02, 1.07]; P = 1.4x10-4). In combined analysis across race/ethnic groups in MESA, rs10846744 was associated with Lp-PLA2 mass (P = 0.04) and activity (P = 0.001), homocysteine (P = 0.03), LDL particle number (P = 0.01), docosahexaenoic acid [DHA] (P = 0.01), docosapentaenoic acid [DPA] (P = 0.04), DPA/ eicosapentaenoic acid [EPA] ratio (P = 0.002), and DHA/EPA ratio (P = 0.008). Lp-PLA2 activity was identified as a mediator of rs10846744 with cIMT in a basic model (P = 8x10-5), but not after adjustment for CVD risk factors. There was no interaction or modifier effect of the Lp-PLA2 inhibitor darapladib assignment on the relationship between rs10846744 and major CVD events in either STABILITY or SOLID-TIMI 52. SCARB1 rs10846744 is significantly associated with Lp-PLA2 activity, atherosclerosis, and CVD events, but Lp-PLA2 activity is not a mediator in the association of rs10846744 with cIMT in MESA.
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影响因子：
4.5
作者：
Suchindran S;Rivedal D;Guyton JR;Milledge T;Gao X;Benjamin A;Rowell J;Ginsburg GS;McCarthy JJ
通讯作者：
McCarthy JJ
DOI：
10.1161/circgenetics.108.829747
发表时间：
2009-02
期刊：
Circulation. Cardiovascular genetics
影响因子：
--
作者：
Psaty BM;O'Donnell CJ;Gudnason V;Lunetta KL;Folsom AR;Rotter JI;Uitterlinden AG;Harris TB;Witteman JC;Boerwinkle E;CHARGE Consortium
通讯作者：
CHARGE Consortium
DOI：
10.1093/bioinformatics/btq340
发表时间：
2010-09-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Willer CJ;Li Y;Abecasis GR
通讯作者：
Abecasis GR
影响因子：
37.8
作者：
Yeboah J;Folsom AR;Burke GL;Johnson C;Polak JF;Post W;Lima JA;Crouse JR;Herrington DM
通讯作者：
Herrington DM
影响因子：
5
作者：
Bild, DE;Bluemke, DA;Tracy, RP
通讯作者：
Tracy, RP