title: Plasma proprotein convertase subtilisin/kexin type 9 is associated with Lp(a) in type 2 diabetic patients.
abstract: OBJECTIVE
  Recent in vitro researches have shown that plasma Lp(a) can be reduced using a proprotein convertase subtilisin/kexin type 9 (PCSK9)-inhibitory monoclonal antibody. In our clinical study we tried to investigate the association between plasma Lp(a) and PCSK9 in Type 2 diabetic patients with elevated plasma Lp(a), and to check whether such an association would be related to LDL-receptor (LDL-R) levels.
  
  
  METHODS
  Plasma PCSK9 and LDL-R concentrations were measured by sandwich ELISA methods using recombinant human PCSK9 protein and LDL-R protein as standards in a cohort with type 2 diabetic patients (n=50) compared to an age- and sex-matched control group (n=50). Both clinical and biochemical parameters were determined in all patients.
  
  
  RESULTS
  Plasma PCSK9 level was significantly elevated in T2DM patients compared to controls (44.61±14.44 and 33.22±11.79ng/mL, respectively, P<0.0001). However LDL-R levels did not differ between the two groups. Remarkably, plasma PCSK9 levels were positively correlated with Lp(a) levels in whole population (r=+0.227, P=0.03) as well as in T2DM group (r=+0.398, P=0.0061) but not in control group. Multiple linear regression analysis showed that plasma Lp(a) levels were independently associated to those of PCSK9.
  
  
  CONCLUSIONS
  Lp(a) has been proposed as a contributing factor to the accelerated development of macrovascular complications in T2DM. Its synergic effect with PCSK9 may explain the enhanced atherogenicity in T2DM patients.
authors.affiliation: UR11ES33'Integrated Physiology', Faculty of Sciences of Bizerte, Carthage University, Tunisia.
authors.forename: Ymène
authors.initials: Y
authors.lastname: Nekaies
authors.affiliation: Biochemistry Department, Biology and Pathology Pole HUEP, Saint-Antoine Hospital, Paris and UMR INSERM S1193, Faculty of Pharmacy - Paris Sud University, Châtenay-Malabry, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Baudin
authors.affiliation: Internal Medicine Department, Regional Hospital of Bizerte, Tunisia.
authors.forename: Sami
authors.initials: S
authors.lastname: Kelbousi
authors.affiliation: UR11ES33'Integrated Physiology', Faculty of Sciences of Bizerte, Carthage University, Tunisia.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Sakly
authors.affiliation: UR11ES33'Integrated Physiology', Faculty of Sciences of Bizerte, Carthage University, Tunisia. Electronic address: nebilatt@yahoo.fr.
authors.forename: Nebil
authors.initials: N
authors.lastname: Attia
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D003925:Diabetic Angiopathies / Q000150:complications / Q000453:epidemiology; D050171:Dyslipidemias / Q000150:complications* / Q000453:epidemiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016014:Linear Models; D008055:Lipids / Q000097:blood; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood*; D011973:Receptors, LDL / Q000097:blood; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000097:blood*; D014416:Tunisia / Q000453:epidemiology; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C573412:LDLR protein, human; D008055:Lipids; D017270:Lipoprotein(a); D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: Dyslipidemia; LDL-receptor; Lp(a); Proprotein convertase subtilisin/kexin type 9; Type 2 diabetes mellitus