Carriers of the 460Trp allele of the alpha-adducin gene (ADD1) show higher rates of sodium reabsorption compared with homozygous carriers of the Gly460 allele and were found to have an increased risk of hypertension and cardiovascular disease.
In this short editorial review, we summarize the recent experimental, clinical and epidemiological evidence that contributed to our understanding of the pathogenetic mechanisms that lead to hypertension associated with the alpha-adducinGly460Trp polymorphism and its interaction with ouabain.
Furthermore the identification of genetic polymorphisms in the effectors involved in the pathophysiology of hypertension or in the response to anti-hypertensive drugs, such as the p22phox subunit of NADPH oxidase, alpha-adducin or adrenergic receptors, has promoted the prospective of both better understanding of hypertension and individualized strategies for its treatment.
Our analysis shows that the 460Trp variant of the alpha-adducin polymorphism is probably associated with a sodium-sensitive form of hypertension, while the polymorphisms of the angiotensin II type 1 receptor gene and the -344C/T variant of the aldosterone synthase gene are not associated with this phenotype.
In a prospective analysis of a Caucasian population, we recently found that the genes encoding angiotensin-converting enzyme (ACE, I/D polymorphism), alpha-adducin (Gly460Trp) and aldosterone synthase (-344C/T) jointly influence the incidence of hypertension.
The 1797T allele of the beta-adducin gene is associated with increased risk of hypertension in post-menopausal women and in users of oral contraceptives, particularly in the presence of the mutated alpha-adducin Trp allele.
However, we failed to detect a positive association between the Gly460Trp polymorphism of ADD-1 and hypertension in a small series of Japanese subjects.
However, a test of the interaction between hypertension status and the ADD1G460W polymorphism indicated that further evaluation of the ADD1 polymorphism in only hypertensive individuals was warranted.
We investigated the association between angiotensin-converting enzyme insertion/deletion, angiotensinogen and alpha-adducin polymorphisms with LV mass and plasma renin activity (PRA) in 162 men with mild, never-treated hypertension who were recruited for the Hypertension and Ambulatory Recording Venetia Study.
In this study, 3 physiologically important candidate gene mutations (angiotensinogen A[-6], alpha-AdducinGly460Trp, and G-Protein beta(3)-subunit C825T) were examined for their association with hypertension status in a sample of 904 African Americans from Jackson, Mississippi.
We studied the relationship between the 460-Trp variant of alpha-adducin gene with hypertension using a case-control study design in black South Africans.
Additional studies have suggested that a polymorphism within exon 10 of the human alpha-adducin gene (Gly-460-Trp) may be associated with hypertension and salt sensitivity.