ArticleScientific reports2016
Genome Wide Association Study Identifies L3MBTL4 as a Novel Susceptibility Gene for Hypertension.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- Trial
- Evolutionary history of disease-susceptibility loci identified in longitudinal exome-wide association studies.Molecular genetics & genomic medicine · 2019Trial
- CRISPR screening identifies DTX4 governing alveolar macrophage cholesterol efflux in pulmonary alveolar proteinosis.JCI insight · 2026Article
- Lysine Methylation-Dependent Proteolysis by the Malignant Brain Tumor (MBT) Domain Proteins.International journal of molecular sciences · 2024Review
- Causality of gut microbiome and hypertension: A bidirectional mendelian randomization study.Frontiers in cardiovascular medicine · 2023Article
- Extracellular vesicles in vascular remodeling.Acta pharmacologica Sinica · 2022Review
- p38/JNK Is Required for the Proliferation and Phenotype Changes of Vascular Smooth Muscle Cells Induced byInternational journal of hypertension · 2020Article
- Genome-Wide Association Studies of Hypertension and Several Other Cardiovascular Diseases.Pulse (Basel, Switzerland) · 2019Review
- miRNA Profiling of Exosomes from Spontaneous Hypertensive Rats Using Next-Generation Sequencing.Journal of cardiovascular translational research · 2019Article
- Brief Overview of a Decade of Genome-Wide Association Studies on Primary Hypertension.International journal of endocrinology · 2018Review
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypertension is a major global health burden and a leading risk factor for cardiovascular diseases. Although its heritability has been documented previously, contributing loci identified to date account for only a small fraction of blood pressure (BP) variation, which strongly suggests the existence of undiscovered variants. To identify novel variants, we conducted a three staged genetic study in 21,990 hypertensive cases and normotensive controls. Four single nucleotide polymorphisms (SNPs) at three new genes (L3MBTL4 rs403814, Pmeta = 6.128 × 10(-9); LOC729251, and TCEANC) and seven SNPs at five previously reported genes were identified as being significantly associated with hypertension. Through functional analysis, we found that L3MBTL4 is predominantly expressed in vascular smooth muscle cells and up-regulated in spontaneously hypertensive rats. Rats with ubiquitous over-expression of L3MBTL4 exhibited significantly elevated BP, increased thickness of the vascular media layer and cardiac hypertrophy. Mechanistically, L3MBTL4 over-expression could lead to down-regulation of latent transforming growth factor-β binding protein 1 (LTBP1), and phosphorylation activation of the mitogen-activated protein kinases (MAPK) signaling pathway, which is known to trigger the pathological progression of vascular remodeling and BP elevation. These findings pinpointed L3MBTL4 as a critical contributor to the development and progression of hypertension and uncovers a novel target for therapeutic intervention.
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