Larissa Hiddink1, Geesje M Dallinga-Thie2, G Kees Hovingh2, Marieke C H de Visser3, Petronella G M Peer3, Anton F H Stalenhoef4, Waander L van Heerde5. 1. Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands. 2. Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. 3. Department for Health Evidence, Radboud University Medical Center, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands. 4. Department of General Internal Medicine, Radboud University Medical Center, Geert Grooteplein 8, 6525 GA Nijmegen, The Netherlands. 5. 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.
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.
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 FHpatients 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 FHpatients 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 FHpatients.
Authors: Ajibola Adedayo; Ayobami Eluwole; Fasika Tedla; Arye Kremer; Muhammad Khan; Nicole Mastrogiovanni; Carl Rosenberg; Paul Dreizen; John La Rosa; Louis Salciccioli; Mohamed Boutjdir; Mary Ann Banerji; Clinton Brown; Jason Lazar; Moro Salifu; Ahmed Bakillah Journal: Biomedicines Date: 2022-07-28