title: SULF2 strongly prediposes to fasting and postprandial triglycerides in patients with obesity and type 2 diabetes mellitus.
abstract: 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.
authors: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: H Carlijne
authors: HC
authors: Hassing
authors: R Preethi
authors: RP
authors: Surendran
authors: Bruno
authors: B
authors: Derudas
authors: An
authors: A
authors: Verrijken
authors: Sven M
authors: SM
authors: Francque
authors: Hans L
authors: HL
authors: Mooij
authors: Sophie J
authors: SJ
authors: Bernelot Moens
authors: Leen M 't
authors: LM
authors: Hart
authors: Giel
authors: G
authors: Nijpels
authors: Jacqueline M
authors: JM
authors: Dekker
authors: Kevin Jon
authors: KJ
authors: Williams
authors: Erik S G
authors: ES
authors: Stroes
authors: Luc F
authors: LF
authors: Van Gaal
authors: Bart
authors: B
authors: Staels
authors: Max
authors: M
authors: Nieuwdorp
authors: Geesje M
authors: GM
authors: Dallinga-Thie
mesh_terms: D000368:Aged; D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000235:genetics; D050171:Dyslipidemias / Q000097:blood; D005215:Fasting; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000502:physiology; D019518:Postprandial Period; D011446:Prospective Studies; D013429:Sulfatases; D015238:Sulfotransferases / Q000235:genetics*; D014280:Triglycerides / Q000097:blood*
chemical_list: D014280:Triglycerides; D015238:Sulfotransferases; C470792:SULF2 protein, human; D013429:Sulfatases