ArticlePloS one2016
LDLR and PCSK9 Are Associated with the Presence of Antiphospholipid Antibodies and the Development of Thrombosis in aPLA Carriers.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- The association of the PCSK9 rs562556 polymorphism with serum lipids level: a meta-analysis.Lipids in health and disease · 2019Pooled it
- PCSK9 in T-cell function and the immune response.Biomarker research · 2024Review
- An immunogenomic exome landscape of triple positive primary antiphospholipid patients.Genes and immunity · 2024Article
- The Link between miRNAs and PCKS9 in Atherosclerosis.Current medicinal chemistry · 2024Review
- Identification of LDLR mutation in cerebral venous sinus thrombosis co-existing with dural arteriovenous fistulas: a case report.BMC neurology · 2023Article
- The Anti-Thrombotic Effects of PCSK9 Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Pleiotropic Effects of PCSK9: Focus on Thrombosis and Haemostasis.Metabolites · 2022Review
- Proteomic Profiling of Cryoglobulinemia.Frontiers in immunology · 2022Article
- PCSK9 Induces Tissue Factor Expression by Activation of TLR4/NFkB Signaling.International journal of molecular sciences · 2021Article
- PCSK9 Functions in Atherosclerosis Are Not Limited to Plasmatic LDL-Cholesterol Regulation.Frontiers in cardiovascular medicine · 2021Review
- Genetics of Antiphospholipid Syndrome.Current rheumatology reports · 2019Review
- The role of proprotein convertase subtilisin-kexin type 9 (PCSK9) in the vascular aging process - is there a link?Kardiochirurgia i torakochirurgia polska = Polish journal of cardio-thoracic surgery · 2019Review
- Polymorphisms in PCSK9, LDLR, BCMO1, SLC12A3, and KCNJ1 are Associated with Serum Lipid Profile in Chinese Han Population.International journal of environmental research and public health · 2019Article
- Multilocus Analysis of Genetic Susceptibility to Myocardial Infarction in Russians: Replication Study.Acta naturaeArticle
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe identification of the genetic risk factors that could discriminate non- thrombotic from thrombotic antiphospholipid antibodies (aPLA) carriers will improve prognosis of these patients. Several human studies have shown the presence of aPLAs associated with atherosclerotic plaque, which is a known risk factor for thrombosis. Hence, in order to determine the implication of atherosclerosis in the risk of developing thrombosis in aPLA positive patients, we performed a genetic association study with 3 candidate genes, APOH, LDLR and PCSK9. MATERIAL &
methodsFor genetic association study we analyzed 190 aPLA carriers -100 with non-thrombotic events and 90 with thrombotic events- and 557 healthy controls. Analyses were performed by χ2 test and were corrected by false discovery rate. To evaluate the functional implication of the newly established susceptibility loci, we performed expression analyses in 86 aPLA carrier individuals (43 with thrombotic manifestations and 43 without it) and in 45 healthy controls.
resultsOur results revealed significant associations after correction in SNPs located in LDLR gene with aPLA carriers and thrombotic aPLA carriers, when compared with healthy controls. The most significant association in LDLR gene was found between SNP rs129083082 and aPLA carriers in recessive model (adjusted P-value = 2.55 x 10-3; OR = 2.18; 95%CI = 1.49-3.21). Furthermore, our work detected significant allelic association after correction between thrombotic aPLA carriers and healthy controls in SNP rs562556 located in PCSK9 gene (adjusted P-value = 1.03 x 10-2; OR = 1.60; 95%CI = 1.24-2.06). Expression level study showed significantly decreased expression level of LDLR gene in aPLA carriers (P-value <0.0001; 95%CI 0.16-2.10; SE 0.38-1.27) in comparison to the control group. DISCUSSION: Our work has identified LDLR gene as a new susceptibility gene associated with the development of thrombosis in aPLA carriers, describing for the first time the deregulation of LDLR expression in individuals with aPLAs. Besides, thrombotic aPLA carriers also showed significant association with PCSK9 gene, a regulator of LDLR plasma levels. These results highlight the importance of atherosclerotic processes in the development of thrombosis in patients with aPLA.
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