Chromatin State Maps of Blood Pressure-Relevant Renal Segments Reveal Potential Regulatory Role for SNPs.
Document Type
Article
Publication Date
3-1-2025
Original Citation
Ray A,
Yang C,
Stelloh C,
Tutaj M,
Liu P,
Liu Y,
Qiu Q,
Auer P,
Lin C,
Widlansky M,
Geurts A,
Cowley A,
Liang M,
Kwitek A,
Greene A,
Rao S.
Chromatin State Maps of Blood Pressure-Relevant Renal Segments Reveal Potential Regulatory Role for SNPs. Hypertension. 2025;82(3):476-88.
Keywords
JMG, Polymorphism, Single Nucleotide, Humans, Chromatin, Blood Pressure, Animals, Rats, Hypertension, Genome-Wide Association Study, Male, Kidney Tubules, Proximal, Kidney, Female
JAX Source
Hypertension. 2025;82(3):476-88.
ISSN
1524-4563
PMID
39723540
DOI
https://doi.org/10.1161/HYPERTENSIONAHA.124.23873
Abstract
BACKGROUND: Hypertension or elevated blood pressure (BP) is a worldwide clinical challenge and the leading primary risk factor for kidney dysfunctions, heart failure, and cerebrovascular disease. The kidney is a central regulator of BP by maintaining sodium-water balance. Multiple genome-wide association studies revealed that BP is a heritable quantitative trait, modulated by several genetic, epigenetic, and environmental factors. The SNPs identified in genome-wide association studies predominantly (>95%) reside within noncoding genomic regions, making it difficult to understand how they regulate BP. Given the central role of the kidney in regulating BP, we hypothesized that chromatin-accessible regions in renal tissue would be enriched for BP-associated single nucleotide polymorphisms.
METHODS: We manually dissected 2 important kidney segments that maintain the sodium-water balance: proximal tubules and medullary thick ascending limbs from the human and rat kidneys. To delineate their chromatin and transcriptomic profiles, we performed the assay for transposase-accessible chromatin and RNA sequencing, respectively.
RESULTS: The chromatin accessibility maps revealed the shared and unique
CONCLUSIONS: Collectively, this study lays a foundation for interrogating how intergenic single nucleotide polymorphisms may regulate polygenic traits such as BP.