rs4961

rs4961 is a variation in the adducin 1 ADD1 gene, encoding a change from a glycine to a tryptophan, so it is also known as G460W or Gly460Trp. 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. 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. 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. 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. 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). rs4961 is in strong linkage with rs4963 (also known as S586C), another ADD1 gene SNP. Ten renin-angiotensin system-related gene polymorphisms in maximally treated Canadian Caucasian patients with heart failure. Relationships among endogenous ouabain, alpha-adducin polymorphisms and renal sodium handling in primary hypertension. New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background. Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations. Arterial properties in relation to genetic variations in the adducin subunits in a white population. A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients. [Association of the polymorphisms of sodium transport related genes with essential hypertension]. Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach. Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women's Genome Health Study. Development of a fingerprinting panel using medically relevant polymorphisms. A candidate gene association study of 77 polymorphisms in migraine. Novel genetic variants in the alpha-adducin and guanine nucleotide binding protein beta-polypeptide 3 genes and salt sensitivity of blood pressure. Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project. A study of ACE and ADD1 polymorphism in ischemic and hemorrhagic stroke. Do ACE (rs4646994) and alphaADDUCIN (rs4961) gene polymorphisms predict the recurrence of hypertensive intracerebral hemorrhage?