Genetic variation in SULF2 is associated with postprandial clearance of triglyceride-rich remnant particles and triglyceride levels in healthy subjects.
Genetic variation in SULF2 is associated with postprandial clearance of triglyceride-rich remnant particles and triglyceride levels in healthy subjects.
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DOI：
10.1371/journal.pone.0079473
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Borén J
中科院分区：
文献类型：
--
作者：
Matikainen N;Burza MA;Romeo S;Hakkarainen A;Adiels M;Folkersen L;Eriksson P;Lundbom N;Ehrenborg E;Orho-Melander M;Taskinen MR;Borén J
非空腹（餐后）甘油三酯浓度已成为临床上显著的心血管疾病风险因素，其由循环中残留的富含甘油三酯的脂蛋白（TRL）蓄积引起。残留的TRL通过肝脏摄取从循环中清除，但涉及的具体机制尚不清楚。多配体蛋白聚糖-1硫酸乙酰肝素蛋白聚糖（HSPG）途径对于小鼠中残留TRL的肝脏清除非常重要，但其在人体中的相关性尚不清楚。 我们试图确定负责HSPG组装和拆卸的基因多态性是否有助于人类致动脉粥样硬化性血脂异常。 我们在68名健康受试者中进行了口服脂肪负荷。从血液中分离脂蛋白（乳糜微粒和极低密度脂蛋白1和2），计算餐后变量的曲线下面积和曲线下面积增量。在研究对象中，编码syndecan-1和参与HSPG合成或降解的酶的基因的单核苷酸多态性被分型。我们的研究结果表明，SULF 2的遗传变异rs 2281279与健康受试者餐后残留TRL和甘油三酯水平的清除有关。此外，SULF 2中的SNP rs 2281279与肝脏SULF 2 mRNA水平相关。在人类中，轻度但临床相关的餐后高脂血症，由于减少肝脏清除残余TRL可能会导致影响肝脏HSPG的遗传多态性。
Nonfasting (postprandial) triglyceride concentrations have emerged as a clinically significant cardiovascular disease risk factor that results from accumulation of remnant triglyceride-rich lipoproteins (TRLs) in the circulation. The remnant TRLs are cleared from the circulation by hepatic uptake, but the specific mechanisms involved are unclear. The syndecan-1 heparan sulfate proteoglycan (HSPG) pathway is important for the hepatic clearance of remnant TRLs in mice, but its relevance in humans is unclear. We sought to determine whether polymorphisms of the genes responsible for HSPG assembly and disassembly contribute to atherogenic dyslipoproteinemias in humans. We performed an oral fat load in 68 healthy subjects. Lipoproteins (chylomicrons and very low density lipoproteins 1 and 2) were isolated from blood, and the area under curve and incremental area under curve for postprandial variables were calculated. Single nucleotide polymorphisms in genes encoding syndecan-1 and enzymes involved in the synthesis or degradation of HSPG were genotyped in the study subjects. Our results indicate that the genetic variation rs2281279 in SULF2 associates with postprandial clearance of remnant TRLs and triglyceride levels in healthy subjects. Furthermore, the SNP rs2281279 in SULF2 associates with hepatic SULF2 mRNA levels. In humans, mild but clinically relevant postprandial hyperlipidemia due to reduced hepatic clearance of remnant TRLs may result from genetic polymorphisms that affect hepatic HSPG.
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影响因子：
3.4
作者：
Jackson, Veronica;Petrini, Johan;Franco-Cereceda, Anders
通讯作者：
Franco-Cereceda, Anders
影响因子：
15.9
作者：
Fuki, IV;Kuhn, KM;Williams, KJ
通讯作者：
Williams, KJ
影响因子：
64.8
作者：
Skålén, K;Gustafsson, M;Borén, J
通讯作者：
Borén, J
影响因子：
5.7
作者：
Folkersen, Lasse;Wagsater, Dick;Eriksson, Per
通讯作者：
Eriksson, Per
影响因子：
15.9
作者：
MacArthur, Jennifer M.;Bishop, Joseph R.;Esko, Jeffrey D.
通讯作者：
Esko, Jeffrey D.