|(G;T)||2||1.8x increased risk for high blood pressure|
|(T;T)||2.1||1.8x increased risk for high blood pressure|
Originally, a study of 477 Italian patients indicated that carriers of one or two rs4961(T) alleles were at 1.8x increased risk for hypertension (CI: 1.32-2.43). This study also indicated that carriers of the risk (T) allele responded better to diuretics and sodium-restricted diets, in that they tended to lower their blood pressure by ~10 mmHg points compared to rs4961(G;G) homozygotes similarly treated.[PMID 9149697]
Subsequent studies have tended to confirm this association, and to extend it to risk for heart disease. They also have tended to confirm that risk allele carriers respond better to therapy.
In a study of ~2200 Belgian patients, rs4961(T) carriers were generally at 2-3 fold higher rik for cardiovascular mortality and morbidity.[PMID 16043664]
In a study of ~1000 hypertensives followed for 10 years, rs4961(T) carriers responded better to low-dose diuretic therapy, as seen by a lower (almost halved) risk of combined myocardial infarction or stroke than if other antihypertensive therapies were used to achieve the same reduction in blood pressure.[PMID 11926892]
A SNP in another adducin gene, adducin 3 ADD3, may modify the risk of carrying an rs4961 risk allele. Carriers of an rs4961(T) allele who are also rs3731566(G;G) homozygotes have higher systolic and diastolic blood pressure, by about 8 mmHg, compared to if they have another rs3731566 genotype.[PMID 15716695]
[PMID 19927152] Accumulation of common polymorphisms is associated with development of hypertension: a 12-year follow-up from the Ohasama study
[PMID 19960031] Lack of association between alpha-adducin G460W polymorphism and hypertension: evidence from a case-control study and a meta-analysis
[PMID 20145305] Association between α-adducin gene polymorphism (Gly460Trp) and genetic predisposition to salt sensitivity: a meta-analysis
[PMID 19838659] alpha- and beta-Adducin polymorphisms affect podocyte proteins and proteinuria in rodents and decline of renal function in human IgA nephropathy
[PMID 21291465] The association of genetic polymorphisms with cerebral palsy: a meta-analysis
[PMID 21339657] Angiotensin-converting enzyme (rs4646994) and ? ADDUCIN (rs4961) gene polymorphisms' study in primary spontaneous intracerebral hemorrhage
|Disease||Hypertension furosemide and spironolactone response - Efficacy|
|CLNDBN||Hypertension, salt-sensitive essential, susceptibility to furosemide and spironolactone response - Efficacy|
|CLNSRC||OMIM Allelic Variant PharmGKB Clinical Annotation UniProtKB (protein)|
[PMID 18279468] Ten renin-angiotensin system-related gene polymorphisms in maximally treated Canadian Caucasian patients with heart failure.
[PMID 18398333] Relationships among endogenous ouabain, alpha-adducin polymorphisms and renal sodium handling in primary hypertension.
[PMID 18513389] New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.
[PMID 18660489] Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations.
[PMID 18787518] Arterial properties in relation to genetic variations in the adducin subunits in a white population.
[PMID 19131662] A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients.
[PMID 19199261] [Association of the polymorphisms of sodium transport related genes with essential hypertension].
[PMID 19263529] Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach.
[PMID 19330901] Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women's Genome Health Study.
[PMID 19379518] Development of a fingerprinting panel using medically relevant polymorphisms.
[PMID 19559392] A candidate gene association study of 77 polymorphisms in migraine.
[PMID 19574959] Novel genetic variants in the alpha-adducin and guanine nucleotide binding protein beta-polypeptide 3 genes and salt sensitivity of blood pressure.
[PMID 20565774] Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.
[PMID 21194526] A study of ACE and ADD1 polymorphism in ischemic and hemorrhagic stroke.
[PMID 22198647] Do ACE (rs4646994) and alphaADDUCIN (rs4961) gene polymorphisms predict the recurrence of hypertensive intracerebral hemorrhage?
|qualified_impact||Insufficiently evaluated pathogenic|
|summary||This variant is associated with salt-sensitivity in patients with hypertension.|
[PMID 23122309] The relationship between polymorphisms at 17 gene sites and hypertension among the Aboriginal Tibetan people
[PMID 22810272] Computational study of ADD1 gene polymorphism associated with hypertension.
[PMID 27480094] Association of interactions between dietary salt consumption and hypertension-susceptibility genetic polymorphisms with blood pressure among Japanese male workers.