title: Impact of serum amyloid A on cellular cholesterol efflux to serum in type 2 diabetes mellitus.
abstract: OBJECTIVE
  Serum amyloid A (SAA) is an acute phase response protein and has apolipoprotein properties. Since type 2 diabetes is associated with chronic subclinical inflammation, the objective of this study is to investigate the changes in SAA level in type 2 diabetic patients and to evaluate the relationship between SAA and the capacity of serum to induce cellular cholesterol efflux via the two known cholesterol transporters, scavenger receptor class B type I (SR-BI) and ATP-binding cassette transporter G1 (ABCG1).
  
  
  METHODS
  264 patients with type 2 diabetes mellitus (42% with normoalbuminuria, 30% microalbuminuria, and 28% proteinuria) and 275 non-diabetic controls were recruited. SAA was measured by ELISA. SR-BI and ABCG1-mediated cholesterol efflux to serum were determined by measuring the transfer of [(3)H]cholesterol from Fu5AH rat hepatoma cells expressing SR-BI and from human ABCG1-transfected CHO-K1 cells to the medium containing the tested serum respectively.
  
  
  RESULTS
  SAA was significantly increased in diabetic patients with incipient or overt nephropathy. Both SR-BI and ABCG1-mediated cholesterol efflux to serum were significantly impaired in all three groups of diabetic patients (p < 0.01). SAA inversely correlated with SR-BI-mediated cholesterol efflux (r = -0.36, p < 0.01) but did not correlate with ABCG1-mediated cholesterol efflux. Stepwise linear regression analysis showed that HDL, the presence or absence of diabetes, and log(SAA) were significant independent determinants of SR-BI-mediated cholesterol efflux to serum.
  
  
  CONCLUSIONS
  SAA was increased in type 2 diabetic patients with incipient or overt nephropathy, and SAA was associated with impairment of SR-BI-mediated cholesterol efflux to serum.
authors.affiliation: Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong.
authors.forename: J G S
authors.initials: JG
authors.lastname: Tsun
authors.forename: S W M
authors.initials: SW
authors.lastname: Shiu
authors.forename: Y
authors.initials: Y
authors.lastname: Wong
authors.forename: S
authors.initials: S
authors.lastname: Yung
authors.forename: T M
authors.initials: TM
authors.lastname: Chan
authors.forename: K C B
authors.initials: KC
authors.lastname: Tan
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000097:blood*; D000328:Adult; D000368:Aged; D000818:Animals; D001053:Apolipoproteins / Q000097:blood*; D016466:CHO Cells; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D006224:Cricetinae; D003412:Cricetulus; D048909:Diabetes Complications / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D051381:Rats; D051122:Scavenger Receptors, Class B / Q000097:blood*; D000685:Serum Amyloid A Protein / Q000378:metabolism*
chemical_list: C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D001053:Apolipoproteins; D008076:Cholesterol, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D000685:Serum Amyloid A Protein; D002784:Cholesterol
keywords: ATP-binding cassette transporter G1; Cellular cholesterol efflux; High density lipoprotein; Reverse cholesterol transport; Scavenger receptor class B type I; Serum amyloid A