A Consideration of Genetic Mechanisms Behind the Development of Hypertension in Blacks

Abstract

Hypertension is a more serious disease in blacks. The determinants of the blood pressure (BP) may be uniquely different from those in whites. The characteristic low-renin, salt-sensitive hypertension of blacks is consistent with the kidney reabsorbing additional sodium (Na), which leads to an expanded plasma volume that drives the BP. Mechanisms considered are genetically based. These include: (1) the intra-renal renin-angiotensin system (RAS), one based on molecular variations in angiotensinogen; (2) the Na, K, 2Cl cotransporter (NKCC2) and its regulators in the thick ascending limb, which are associated with a variety of phenotypes consistent with a more active cotransporter in blacks; and (3) the genes for MYH9 and APOL 1, which have been associated with kidney disease in blacks. To achieve a state of hypertension, an increase in Na uptake in proximal nephron regions may require a distal nephron that does not fully adjust due to less than adequate suppression of aldosterone production.

Hypertension and ethnicity

“…Numerous studies have outlined the possible genetic contributors to HTN among blacks [26][27][28][29][30]. Blacks exhibit low renin levels, leading to additional sodium reabsorption by the kidneys, which in turn contributes to elevated BP [26,27].…”

“…Blacks exhibit low renin levels, leading to additional sodium reabsorption by the kidneys, which in turn contributes to elevated BP [26,27]. Additionally, a more active sodium-potassiumchloride cotransporter in the thick ascending limb of the kidneys has been associated with multiple phenotypes in blacks [26,27].…”

“…Blacks exhibit low renin levels, leading to additional sodium reabsorption by the kidneys, which in turn contributes to elevated BP [26,27]. Additionally, a more active sodium-potassiumchloride cotransporter in the thick ascending limb of the kidneys has been associated with multiple phenotypes in blacks [26,27]. The reduced bioavailability of nitric oxide in blacks has been shown to contribute to both resting and stimulus-mediated vasodilator tone and elevation in BP compared with whites [27][28][29][30].…”

Dysregulated aldosterone secretion in persons of African descent with endothelin-1 gene variants

“…Tu and Pratt concluded that the low-renin, salt sensitivity of BP phenotype of AD compared with ED is attributed to alterations in genetic makeup (36). They went on to describe greater renal Na + absorption among AD compared with ED, thus leading to expanded plasma volume in this population.…”

Understanding the Importance of Race/Ethnicity in the Care of the Hypertensive Patient

“…In AAs, hypertension is generally considered related to high reabsorption of sodium (Na) and this low-renin, salt-sensitive hypertension may be, at least in part, genetically-based, with a more active Na, potassium (K), 2 chloride cotransporter (NKCC2), and its regulators in the thick ascending limb [25]. Although, urinary excretion of Na appears similar in Blacks and Whites, indicating similar dietary Na intakes, urinary excretion of K is generally lower in AAs [26].…”