Natural genetic variants in the 3’ untranslated region of NPPA, the gene that encodes the vasodilator atrial natriuretic peptide (ANP), have previously been linked to blood pressure. Pankaj Arora and colleagues found that individuals with the AG genotype had up to 50% higher levels of ANP when fed a high salt diet compared to individuals with the AA genotype. Additionally, they identified a microRNA, miR-425, that is expressed in human atria and ventricles. Arora and colleagues demonstrated that miR-425 silenced NPPA mRNA encoded by the A allele, but not the G allele. These findings indicate that therapeutics targeting miR-425 could potentially be used to increase ANP levels to treat salt-induced hypertension.
Numerous common genetic variants have been linked to blood pressure, but no underlying mechanism has been elucidated. Population studies have revealed that the variant rs5068 (A/G) in the 3′ untranslated region of
Pankaj Arora, Connie Wu, Abigail May Khan, Donald B. Bloch, Brandi N. Davis-Dusenbery, Anahita Ghorbani, Ester Spagnolli, Andrew Martinez, Allicia Ryan, Laurel T. Tainsh, Samuel Kim, Jian Rong, Tianxiao Huan, Jane E. Freedman, Daniel Levy, Karen K. Miller, Akiko Hata, Federica del Monte, Sara Vandenwijngaert, Melissa Swinnen, Stefan Janssens, Tara M. Holmes, Emmanuel S. Buys, Kenneth D. Bloch, Christopher Newton-Cheh, Thomas J. Wang