The ADD1 1378 G>T (Gly460Trp) polymorphism genetic test analyzes a specific variation in the ADD1 gene, which encodes alpha-adducin, a cytoskeletal protein involved in ion transport, membrane stability, and vascular function. This test detects a guanine (G) to thymine (T) substitution at nucleotide position 1378, resulting in an amino acid change from glycine (Gly) to tryptophan (Trp) at position 460. This genetic variation has been associated with altered sodium handling, blood pressure regulation, and susceptibility to essential hypertension. As α-adducin plays a key role in renal sodium reabsorption and vascular homeostasis, variations in ADD1 influence salt sensitivity, cardiovascular function, and the risk of hypertensive disorders.
Adducin is a structural protein that regulates actin cytoskeleton remodeling and interacts with the sodium-potassium ATPase (Na+/K+-ATPase) pump in renal tubular cells. The Gly460Trp polymorphism has been linked to increased sodium reabsorption in the kidneys, leading to higher extracellular fluid volume and elevated blood pressure. Studies suggest that individuals carrying the T allele exhibit enhanced Na+/K+-ATPase activity, increasing salt retention and a higher predisposition to salt-sensitive hypertension. This effect is particularly significant in individuals with high sodium intake, where the genetic influence of ADD1 contributes to impaired blood pressure regulation and an increased risk of cardiovascular complications.
Hypertension is a multifactorial condition influenced by genetic and environmental factors, with the ADD1 Gly460Trp polymorphism playing a significant role in blood pressure variability. The T allele has been associated with higher systolic and diastolic blood pressure levels and an increased response to antihypertensive therapies targeting sodium excretion, such as diuretics. Studies have demonstrated that individuals carrying the risk allele may benefit more from diuretic-based treatment strategies, suggesting a pharmacogenetic influence of ADD1 on antihypertensive drug response.
Beyond hypertension, the ADD1 Gly460Trp polymorphism has been investigated in relation to cardiovascular diseases, including stroke, left ventricular hypertrophy, and arterial stiffness. Increased sodium retention and vascular remodeling associated with the T allele contribute to endothelial dysfunction, arterial rigidity, and an elevated risk of cerebrovascular events. Additionally, this polymorphism has been linked to metabolic syndrome, insulin resistance, and obesity-related hypertension, reflecting the broader physiological impact of ADD1 on cardiovascular and metabolic health.
Genetic testing for the ADD1 1378 G>T (Gly460Trp) polymorphism provides insight into an individual’s genetic predisposition to hypertension, salt sensitivity, and cardiovascular disease. Identifying this variant allows assessing sodium regulation, blood pressure control, and therapeutic response to antihypertensive treatments.
The ADD1 1378 G>T (Gly460Trp) polymorphism genetic test is also included in:
