ArticleHuman molecular genetics2007
An ancestral variant of Secretogranin II confers regulation by PHOX2 transcription factors and association with hypertension.
Article in Human molecular genetics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Genomic Exploration of Essential Hypertension in African-Brazilian Quilombo Populations: A Comprehensive Approach With Pedigree Analysis and Family-Based Association Studies.Journal of the American Heart Association · 2025Article
- Evolution of Human-Specific Alleles Protecting Cognitive Function of Grandmothers.Molecular biology and evolution · 2022Article
- Identification of candidate biomarkers and therapeutic agents for heart failure by bioinformatics analysis.BMC cardiovascular disorders · 2021Article
- The Emerging Roles of Chromogranins and Derived Polypeptides in Atherosclerosis, Diabetes, and Coronary Heart Disease.International journal of molecular sciences · 2021Review
- Genetic Variants in Transcription Factor Binding Sites in Humans: Triggered by Natural Selection and Triggers of Diseases.International journal of molecular sciences · 2021Review
- ARMC 5 Variants and Risk of Hypertension in Blacks: MH- GRID Study.Journal of the American Heart Association · 2019Article
- Genetics of Hypertension in African Americans and Others of African Descent.International journal of molecular sciences · 2019Review
- Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Genome-wide joint analysis of single-nucleotide variant sets and gene expression for hypertension and related phenotypes.BMC proceedings · 2016Article
- Zfp423 binds autoregulatory sites in p19 cell culture model.PloS one · 2013Article
- The regulated secretory pathway and human disease: insights from gene variants and single nucleotide polymorphisms.Frontiers in endocrinology · 2013Article
- The extended granin family: structure, function, and biomedical implications.Endocrine reviews · 2011Review
- Catecholamine storage vesicles: role of core protein genetic polymorphisms in hypertension.Current hypertension reports · 2011Article
- Genome-wide case/control studies in hypertension: only the 'tip of the iceberg'.Journal of hypertension · 2010Article
- Common functional genetic variants in catecholamine storage vesicle protein promoter motifs interact to trigger systemic hypertension.Journal of the American College of Cardiology · 2010Article
- Pro-hormone secretogranin II regulates dense core secretory granule biogenesis in catecholaminergic cells.The Journal of biological chemistry · 2010Article
- Human dopamine beta-hydroxylase (DBH) regulatory polymorphism that influences enzymatic activity, autonomic function, and blood pressure.Journal of hypertension · 2010Article
- Hereditary determinants of human hypertension: strategies in the setting of genetic complexity.Hypertension (Dallas, Tex. : 1979) · 2008Review
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Authors and funding
15 authors at 9 institutions in 3 countries.
Funding
Abstract
Granins regulate secretory vesicle formation in neuroendocrine cells and granin-derived peptides are co-released with neurotransmitters as modulatory signals at sympathetic sites. We report evidence for association between a regulatory polymorphism in Secretogranin II (SCG2) and hypertension in African-American subjects. The minor allele is ancestral in the human lineage and is associated with disease risk in two case-control studies and with elevated blood pressure in a separate familial study. Mechanistically, the ancestral allele acts as a transcriptional enhancer in cells that express endogenous Scg2, whereas the derived allele does not. ARIX (PHOX2A) and PHOX2B are identified as potential transactivating factors by oligonucleotide affinity chromatography and mass spectrometry and confirmed by chromatin immunoprecipitation. Each of these transcription factors preferentially binds the risk allele, both in vitro and in vivo. Population genetic considerations suggest positive selection of the protective allele within the human lineage. These results identify a common regulatory variation in SCG2 and implicate granin gene expression in the control of human blood pressure and susceptibility to hypertension.
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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.