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Genetic Variation in SULF2 Is Associated with Postprandial Clearance of Triglyceride-Rich Remnant Particles and Triglyceride Levels in Healthy Subjects

Matikainen, Niina; Burza, Maria Antonella; Romeo, Stefano; Hakkarainen, Antti; Adiels, Martin; Folkersen, Lasse; Eriksson, Per; Lundbom, Nina; Ehrenborg, Ewa and Orho-Melander, Marju LU , et al. (2013) In PLoS ONE 8(11).
Abstract
Context: 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. Objective: We sought to determine whether polymorphisms of the genes responsible for HSPG assembly and disassembly contribute to atherogenic dyslipoproteinemias in humans. Patients And Design: We performed an oral fat load in 68... (More)
Context: 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. Objective: We sought to determine whether polymorphisms of the genes responsible for HSPG assembly and disassembly contribute to atherogenic dyslipoproteinemias in humans. Patients And Design: 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. Results: 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. Conclusions: In humans, mild but clinically relevant postprandial hyperlipidemia (Less)
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PLoS ONE
volume
8
issue
11
publisher
Public Library of Science
external identifiers
  • wos:000327313100025
  • scopus:84894274848
ISSN
1932-6203
DOI
10.1371/journal.pone.0079473
language
English
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yes
id
78612e0c-d567-4c32-9bf1-bafb36f8744d (old id 4272933)
date added to LUP
2014-02-10 12:23:58
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2019-02-20 05:28:55
@article{78612e0c-d567-4c32-9bf1-bafb36f8744d,
  abstract     = {Context: 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. Objective: We sought to determine whether polymorphisms of the genes responsible for HSPG assembly and disassembly contribute to atherogenic dyslipoproteinemias in humans. Patients And Design: 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. Results: 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. Conclusions: In humans, mild but clinically relevant postprandial hyperlipidemia},
  author       = {Matikainen, Niina and Burza, Maria Antonella and Romeo, Stefano and Hakkarainen, Antti and Adiels, Martin and Folkersen, Lasse and Eriksson, Per and Lundbom, Nina and Ehrenborg, Ewa and Orho-Melander, Marju and Taskinen, Marja-Riitta and Boren, Jan},
  issn         = {1932-6203},
  language     = {eng},
  number       = {11},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Genetic Variation in SULF2 Is Associated with Postprandial Clearance of Triglyceride-Rich Remnant Particles and Triglyceride Levels in Healthy Subjects},
  url          = {http://dx.doi.org/10.1371/journal.pone.0079473},
  volume       = {8},
  year         = {2013},
}