title: Annexin A5 haplotypes in familial hypercholesterolemia: lack of association with carotid intima-media thickness and cardiovascular disease risk.
abstract: OBJECTIVE
  Annexin A5 (ANXA5) has been suggested to possess antiatherogenic properties. We investigated whether ANXA5 genetic variations and plasma ANXA5 levels were associated with carotid atherosclerosis and contributed to cardiovascular disease (CVD) risk in patients with familial hypercholesterolemia (FH).
  
  
  METHODS
  We sequenced the promoter region and exon 2 of ANXA5 in 284 FH patients from the ASAP (Atorvastatin versus Simvastatin on Atherosclerosis Progression) trial. Common haplotypes (H) were constructed based on seven single nucleotide polymorphisms (SNPs). We studied whether plasma ANXA5 levels or ANXA5 haplotypes were associated with the extent of atherosclerosis (evaluated by carotid intima-media thickness (IMT). The association between ANXA5 haplotypes and the risk for CVD events was investigated in 1730 FH patients from the GIRaFH (Genetic Identification of Risk factors in Familial Hypercholesterolemia) study.
  
  
  RESULTS
  In ASAP, individuals carrying the ANXA5 haplotype H2 exhibited lower plasma ANXA5 levels, whereas H4 carriers had increased levels of circulating ANXA5 compared to non-carriers. Plasma ANXA5 levels were not associated with carotid IMT. None of the four ANXA5 haplotypes correlated with the age-related IMT progression (ASAP study) or contributed to CVD risk (GIRaFH cohort).
  
  
  CONCLUSIONS
  Both ANXA5 haplotypes and plasma ANXA5 levels were not associated with carotid IMT progression or CVD risk in FH patients.
authors.affiliation: Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands.
authors.forename: Larissa
authors.initials: L
authors.lastname: Hiddink
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Geesje M
authors.initials: GM
authors.lastname: Dallinga-Thie
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.affiliation: Department for Health Evidence, Radboud University Medical Center, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Marieke C H
authors.initials: MC
authors.lastname: de Visser
authors.affiliation: Department for Health Evidence, Radboud University Medical Center, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Petronella G M
authors.initials: PG
authors.lastname: Peer
authors.affiliation: Department of General Internal Medicine, Radboud University Medical Center, Geert Grooteplein 8, 6525 GA Nijmegen, The Netherlands.
authors.forename: Anton F H
authors.initials: AF
authors.lastname: Stalenhoef
authors.affiliation: Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands. Electronic address: Waander.vanHeerde@radboudumc.nl.
authors.forename: Waander L
authors.initials: WL
authors.lastname: van Heerde
mesh_terms: D000367:Age Factors; D000368:Aged; D017304:Annexin A5 / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D008076:Cholesterol, HDL / Q000097:blood; D018450:Disease Progression; D005091:Exons; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D017304:Annexin A5; D015415:Biomarkers; D008076:Cholesterol, HDL
keywords: Annexin A5 gene; Atherosclerosis; Cardiovascular disease; Carotid intima-media thickness; Familial hypercholesterolemia; Haplotype