Genetic variation in the epithelial sodium channel: a risk factor for hypertension in people of African origin.
High blood pressure occurs commonly in individuals of African origin, leading to an increased risk of cardiovascular and end-stage renal disease (ESRD). Black individuals frequently have low plasma renin activity, and their blood pressure responds well to salt reduction, suggesting that abnormalities in renal sodium handling may be important in the etiology of hypertension in this population. The epithelial sodium channel (ENaC) has a central role in sodium transport across membranes, and in the kidney it contributes to the regulation of blood pressure via changes in sodium balance and blood volume. Rare monogenetic disorders have been described in association with hypertension, such as Liddle's syndrome. In addition, other ENaC polymorphisms have also been described, some of which are more common in black individuals. The T594M polymorphism of ENaC occurs exclusively in black individuals and is associated with hypertension in a black South London population. There is preliminary evidence that amiloride is effective as monotherapy in hypertensives with the T594M polymorphism, and a further study is underway to determine whether this is indeed a safe and specific treatment. If so, then amiloride may provide an important new strategy for blood pressure control in affected black hypertensives.
Swift
Pauline A
PA
Blood Pressure Unit, St. George's Hospital Medical School, Cranmer Terrace, London, SW17 0RE, UK. pswift@sghms.ac.uk
Macgregor
Graham A
GA
D000584:Amiloride / Q000627:therapeutic use; D044383:Black People / Q000235:genetics*; D004232:Diuretics / Q000627:therapeutic use; D053503:Epithelial Sodium Channels; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D008131:London / Q000453:epidemiology; D008715:Methionine; D011110:Polymorphism, Genetic; D012307:Risk Factors; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism; D013912:Threonine
D004232:Diuretics; D053503:Epithelial Sodium Channels; D015222:Sodium Channels; D013912:Threonine; D000584:Amiloride; D008715:Methionine