Aging, Environment, & DiseaseHistone Modifications

Epigenetic and dietary regulation of salt-sensitive hypertension

The kidneys are responsible for salt reabsorption in the bodyHypertension (also known as high blood pressure) is a disease that is often heritable and can be a direct consequence of dietary factors.  A high intake of dietary salt is one factor that can potentially affect the expression of genes involved in regulating blood pressure, and thus contributes to the development of hypertension.  The enzyme lysine-specific demethylase 1 (LSD-1) regulates histone methylation by demethylating histone H3 at lysine residues 4 and 9 and is involved in salt-sensitive hypertension, indicating that hypertension has an epigenetic component.

In this paper, Williams et al. investigated expression levels of LSD-1 in mouse models as well as single-nuclear polymorphisms (SNPs) in LSD-1 from different ethnic human populations.  In the mouse study, the WT mice showed a decrease in LSD-1 expression with higher salt intake, compared to lower salt intake, while the LSD-1+/- knockout mice showed little differences in LSD-1 gene expression.  However, the LSD-1+/- knockout mice had low LSD-1 expression in the kidney compared to the WT mice, leading to lower levels of aldosterone and lower activity for salt resorption.

Investigating more into the human population, African-American and Hispanic groups that are carriers of the LSD-1 minor alleles (5 different SNPs analyzed) showed an increase in blood pressure in response to changing from low to high salt intake, as well as decreased aldosterone levels.  However, these findings were not observed as much in the Caucasian group, suggesting a potential epigenetic basis for hypertension in some genetic backgrounds.

This study contributes evidence for environmental factors having an important impact on hypertension through epigenetics and its effect on worldwide population.  Furthermore, environmental factors add another layer of difficulty in finding candidate genes related to blood pressure regulation when investigating hypertension.

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Williams JS, Chamarthi B, Goodarzi MO, Pojoga LH, Sun B, Garza AE, Raby BA, Adler GK, Hopkins PN, Brown NJ, Jeunemaitre X, Ferri C, Fang R, Leonor T, Cui J, Guo X, Taylor KD, Ida Chen YD, Xiang A, Raffel LJ, Buchanan TA, Rotter JI, Williams GH, Shi Y.

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Lam N.

Lam N.

Lam N. received her B.S. in Biochemistry and Molecular Biology at the University of California, Irvine. She enjoys playing the guitar, snowboarding, and rooting for the Green Bay Packers. In the lab, she secretly practices to be the fastest PCR pippetor on this side of the Mississippi!