|(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 ~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]
This SNP is also cited in US patent 10,465,246 (2019), where one of the claims is prescribing a hydrochlorothiazide to a patient as a first line therapy (for high blood pressure), without a beta blocker and without a vasodilator, if the patient carries a rs4961(T).
[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
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[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)|
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