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SULF2 strongly prediposes to fasting and postprandial triglycerides in patients with obesity and type 2 diabetes mellitus
Author(s) -
Hassing H. Carlijne,
Surendran R. Preethi,
Derudas Bruno,
Verrijken An,
Francque Sven M.,
Mooij Hans L.,
Bernelot Moens Sophie J.,
Hart Leen M.'t,
Nijpels Giel,
Dekker Jacqueline M.,
Williams Kevin Jon,
Stroes Erik S. G.,
Van Gaal Luc F.,
Staels Bart,
Nieuwdorp Max,
DallingaThie Geesje M.
Publication year - 2014
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.20682
Subject(s) - postprandial , medicine , type 2 diabetes mellitus , diabetes mellitus , endocrinology , obesity , type 2 diabetes , triglyceride , cholesterol
Objective Hepatic overexpression of sulfatase‐2 (SULF2), a heparan sulfate remodeling enzyme, strongly contributes to high triglyceride (TG) levels in obese, type 2 diabetic (T2DM) db/db mice. Nevertheless, data in humans are lacking. Here, the association of human hepatic SULF2 expression and SULF2 gene variants with TG metabolism in patients with obesity and/or T2DM was investigated. Methods Liver biopsies from 121 obese subjects were analyzed for relations between hepatic SULF2 mRNA levels and plasma TG. Associations between seven SULF2 tagSNPs and TG levels were assessed in 210 obese T2DM subjects with dyslipidemia. Replication of positive findings was performed in 1,316 independent obese T2DM patients. Postprandial TRL clearance was evaluated in 29 obese T2DM subjects stratified by SULF2 genotype. Results Liver SULF2 expression was significantly associated with fasting plasma TG ( r = 0.271; P = 0.003) in obese subjects. The SULF2 rs2281279(A>G) SNP was reproducibly associated with lower fasting plasma TG levels in obese T2DM subjects ( P < 0.05). Carriership of the minor G allele was associated with lower levels of postprandial plasma TG ( P < 0.05) and retinyl esters levels ( P < 0.001). Conclusions These findings implicate SULF2 as potential therapeutic target in the atherogenic dyslipidemia of obesity and T2DM.