A new study led by researchers at the National Institutes of Health (NIH) adds more weight to previous findings implicating variants of the gene ARMC5 in the increased risk of hypertension in blacks. Researchers identified 17 variants in the gene that were associated with high blood pressure in individuals of African decent. Their findings were published in the 3 July 2019 issue of the Journal of the American Heart Association.
“High blood pressure increases a person’s risk for heart disease and stroke,” said Constantine A. Stratakis, M.D., D.Sc., the study’s senior author, in a press release. “The condition is more common among blacks, who also tend to get it at a younger age than whites do, and we are studying the underlying causes of this health disparity,” said Stratakis, who is scientific director at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
About one-third of Americans over 20 have hypertension, according to the Centers for Disease Control and Prevention (CDC). In 2013, the National Health and Nutrition Examination Survey found that 42 percent of blacks have the condition. Other studies have shown blacks get the disease earlier and are more likely to suffer its consequences, which range from coronary artery disease and stroke to dementia and kidney failure.
Previous research has linked the predisposition to hypertension in blacks to retention of salt and water. Researchers think excess aldosterone secretion or hypersensitivity to aldosterone may be to blame. Aldosterone, a hormone made by the adrenal cortex, regulates blood pressure by increasing the amount of salt reabsorbed into the bloodstream by the kidneys and colon, among other organs. It also increases the amount of potassium excreted in the urine and prompts the reabsorption of water along with sodium, increasing blood volume and pressure. Earlier work by the NICHD group linked some variants of ARMC5 in blacks to primary aldosteronism, a condition that causes in which too much of the hormone is produced.
In the current paper, researchers report the findings of a three-part study. First, they performed a genome wide association study (GWAS) on whole exome sequencing data from 1377 blacks from NIH’s Minority Health Genomics and Translational Research Bio-Repository Database and the Genomics, Environmental Factors and Social Determinants of Cardiovascular Disease in African-Americans Study. They found 16 rare variants to be significantly associated with hypertension.
Second, the team replicated its results using data from 3015 people of African decent from the UK Biobank. They found the same 16 variants to be associated with hypertension, but also found another that was associated (rs116201073) with low blood pressure. This was the most common variant and it is one that other researchers have found is limited to people of African descent.
Lastly, they confirmed the protective effect of this last variant. The team reconstructed the rs116201073 variant in kidney and adrenal cortex cell lines and found that it was more active than other variants of the ARMC5 gene. However, the exact function of the ARMC5 gene is unclear, and more work is needed to understand what the gene does and how variants may protect or predispose a person to high blood pressure.
“Collectively, our research suggests that ARMC5 may play an important role in regulating blood pressure in blacks,” said Mihail Zilbermint, M.D., one of the lead authors of the study and an assistant professor of medicine at Johns Hopkins University, in the press release. “Because the gene is linked to primary aldosteronism, ARMC5 may be involved in how the adrenal glands function and with the hormones that are important for regulating blood pressure.”