ArticleFrontiers in genetics2015
PCSK9 variation and association with blood pressure in African Americans: preliminary findings from the HyperGEN and REGARDS studies.
Article in Frontiers in genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- The Role of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Cardiovascular Homeostasis: A Non-Systematic Literature Review.Current cardiology reviews · 2017Pooled it
- The role of PCSK9 in heart failure and other cardiovascular diseases-mechanisms of action beyond its effect on LDL cholesterol.Heart failure reviews · 2024Review
- Sex-Specific Differences in Kidney Function and Blood Pressure Regulation.International journal of molecular sciences · 2024Review
- Proprotein convertase subtilisin/kexin type 9 deficiency in extrahepatic tissues: emerging considerations.Frontiers in pharmacology · 2024Review
- Decoding the mechanism of hypertension through multiomics profiling.Journal of human hypertension · 2023Review
- Article
- Arterial Hypertension: Individual Therapeutic Approaches-From DNA Sequencing to Gender Differentiation and New Therapeutic Targets.Pharmaceutics · 2021Review
- Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Levels and Cardiometabolic Risk Factors: A Population-Based Cohort Study.Frontiers in cardiovascular medicine · 2021Article
- 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
- A phenome-wide association study to discover pleiotropic effects ofNPJ genomic medicine · 2019Article
- Advances in the Genetics of Hypertension: The Effect of Rare Variants.International journal of molecular sciences · 2018Review
- Peripheral vascular atherosclerosis in a novel PCSK9 gain-of-function mutant Ossabaw miniature pig model.Translational research : the journal of laboratory and clinical medicine · 2018Article
- Potential Link Between Proprotein Convertase Subtilisin/Kexin Type 9 and Alzheimer's Disease.International journal of biomedical investigation · 2018Article
- Sickle Cell Trait and the Risk of ESRD in Blacks.Journal of the American Society of Nephrology : JASN · 2017Article
- Plasma PCSK9 level is unrelated to blood pressure and not associated independently with carotid intima-media thickness in hypertensives.Hypertension research : official journal of the Japanese Society of Hypertension · 2016Article
- Association of sickle cell trait with atrial fibrillation: The REGARDS cohort.Journal of electrocardiologyArticle
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Proprotein convertase subtilisin/kexin type 9 (encoded by PCSK9) plays a well-known role in the regulation of low-density lipoprotein (LDL) receptors, and an inhibitor of this enzyme is a promising new therapeutic for hyperlipidemia. Recently, animal and human studies also implicate PCSK9 genetic variation in the regulation of blood pressure. The goal of this study was to examine if common and rare polymorphisms in PCSK9 are associated with blood pressure in an African-American population at high risk for cardiovascular disease. Using genomic data assayed on the Affymetrix 6.0 array (n = 1199) and the Illumina HumanExome Beadchip (n = 1966) from the Hypertension Genetic Epidemiology Network (HyperGEN), we tested the association of PCSK9 polymorphisms with blood pressure. We used linear mixed models and the sequence kernel association test (SKAT) to assess the association of 31 common and 19 rare variants with blood pressure. The models were adjusted for age, sex, center, smoking status, principal components for ancestry and diabetes as fixed effects and family as a random effect. The results showed a marginally significant effect of two genome-wide association study (GWAS) single-nucleotide polymorphisms (SNPs) (rs12048828: β = 1.8, P = 0.05 and rs9730100: β = 1.0, P = 0.05) with diastolic blood pressure (DBP); however these results were not significant after correction for multiple testing. Rare variants were cumulatively associated with DBP (P = 0.04), an effect that was strengthened by restriction to non-synonymous or stop-gain SNPs (P = 0.02). While gene-based results for DBP did not replicate (P = 0.36), we found an association with SBP (P = 0.04) in the Reasons for Geographic And Racial Differences in Stroke study (REGARDS). The findings here suggest rare variants in PCSK9 may influence blood pressure among African Americans, laying the ground work for further validation studies.
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