ArticleHuman molecular genetics2013
A common polymorphism in the LDL receptor gene has multiple effects on LDL receptor function.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- PCSK9 is a critical regulator of the innate immune response and septic shock outcome.Science translational medicine · 2014Trial
- Association of LDLR rs688 Polymorphism With Dyslipidemia in End-Stage Renal Disease: A Case-Control Study.Cureus · 2026Article
- Association of LDLR and SCARB1 gene polymorphisms with hepatocellular carcinoma: a case-control study proposing a 'double-hit' model.Lipids in health and disease · 2026Article
- Association of the rs688 Polymorphism in the Gene Encoding Low-Density Lipoprotein Receptor in Bangladeshi Population With Coronary Artery Disease.Genetics research · 2026Article
- Investigation of the characteristics of LDLR gene rs688 polymorphism and its association with dyslipidemia in patients at high to very high cardiovascular risk.BMC cardiovascular disorders · 2025Article
- Calling and Phasing of Single-Nucleotide and Structural Variants of theInternational journal of molecular sciences · 2023Article
- Mechanism of the Regulation of Plasma Cholesterol Levels by PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- LDLR gene polymorphism (rs688) affects susceptibility to cardiovascular disease in end-stage kidney disease patients.BMC nephrology · 2021Article
- Review
- Proprotein Convertase Subtilisin/Kexin Type 9 Loss-of-Function Is Detrimental to the Juvenile Host With Septic Shock.Critical care medicine · 2020Article
- Phosphatidylinositol-(4,5)-Bisphosphate Regulates Plasma Cholesterol Through LDL (Low-Density Lipoprotein) Receptor Lysosomal Degradation.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Interaction between Sex and LDLR rs688 Polymorphism on Hyperlipidemia among Taiwan Biobank Adult Participants.Biomolecules · 2020Article
- SNP rs688 within the low-density lipoprotein receptor (LDL-R) gene associates with HCV susceptibility.Liver international : official journal of the International Association for the Study of the Liver · 2019Article
- Genetic Polymorphisms Associated with Spontaneous Intracerebral Hemorrhage.International journal of molecular sciences · 2018Review
- Nutrigenetic Contributions to Dyslipidemia: A Focus on Physiologically Relevant Pathways of Lipid and Lipoprotein Metabolism.Nutrients · 2018Review
- The association of lipid metabolism relative gene polymorphisms and ischemic stroke in Han and Uighur population of Xinjiang.Lipids in health and disease · 2017Article
- A review of gigaxonin mutations in giant axonal neuropathy (GAN) and cancer.Human genetics · 2016Review
- Article
- Lipids, blood pressure and kidney update 2015.Lipids in health and disease · 2015Review
- PCSK9 inhibition to reduce cardiovascular disease risk: recent findings from the biology of PCSK9.Current opinion in endocrinology, diabetes, and obesity · 2015Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
A common synonymous single nucleotide polymorphism in exon 12 of the low-density lipoprotein receptor (LDLR) gene, rs688, has been associated with increased plasma total and LDL cholesterol in several populations. Using immortalized lymphoblastoid cell lines from a healthy study population, we confirmed an earlier report that the minor allele of rs688 is associated with increased exon 12 alternative splicing (P < 0.05) and showed that this triggered nonsense-mediated decay (NMD) of the alternatively spliced LDLR mRNA. However, since synonymous single nucleotide polymorphisms may influence structure and function of the encoded proteins by co-translational effects, we sought to test whether rs688 was also functional in the full-length mRNA. In HepG2 cells expressing LDLR cDNA constructs engineered to contain the major or minor allele of rs688, the latter was associated with a smaller amount of LDLR protein at the cell surface (-21.8 ± 0.6%, P = 0.012), a higher amount in the lysosome fraction (+25.7 ± 0.3%, P = 0.037) and reduced uptake of fluorescently labeled LDL (-24.3 ± 0.7%, P < 0.01). Moreover, in the presence of exogenous proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces cellular LDL uptake by promoting lysosomal degradation of LDLR, the minor allele resulted in reduced capacity of a PCSK9 monoclonal antibody to increase LDL uptake. These findings are consistent with the hypothesis that rs688, which is located in the β-propeller region of LDLR, has effects on LDLR activity beyond its role in alternative splicing due to impairment of LDLR endosomal recycling and/or PCSK9 binding, processes in which the β-propeller is critically involved.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.