{{Rsnum
|rsid=4961
|Gene=ADD1
|Chromosome=4
|position=2904980
|Orientation=plus
|ReferenceAllele=G
|MissenseAllele=T
|GMAF=0.2489
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(G;G)
|geno2=(G;T)
|geno3=(T;T)
|Gene_s=ADD1
}}{{ population diversity
| geno1=(G;G)
| geno2=(G;T)
| geno3=(T;T)
| CEU | 62.8 | 33.6 | 3.5
| HCB | 19.3 | 52.6 | 28.1
| JPT | 22.1 | 42.5 | 35.4
| YRI | 93.2 | 6.8 | 0.0
| ASW | 90.9 | 9.1 | 0.0
| CHB | 19.3 | 52.6 | 28.1
| CHD | 22.2 | 53.7 | 24.1
| GIH | 68.3 | 27.7 | 4.0
| LWK | 88.0 | 12.0 | 0.0
| MEX | 68.4 | 24.6 | 7.0
| MKK | 78.8 | 19.2 | 1.9
| TSI | 64.7 | 33.3 | 2.0
| HapMapRevision=28
}}[[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.{{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}}

[[rs4961]] is in strong linkage with [[rs4963]] (also known as S586C), another [[ADD1]] gene SNP.

{{PMID Auto
|PMID=19927152
|Title=Accumulation of common polymorphisms is associated with development of hypertension: a 12-year follow-up from the Ohasama study
}}
{{PMID Auto
|PMID=19960031
|Title=Lack of association between alpha-adducin G460W polymorphism and hypertension: evidence from a case-control study and a meta-analysis
}}

{{PharmGKB
|RSID=rs4961
|Name_s=ADD1:Gly460Trp, rs4961 G>T, alpha-adducin Gly460Trp
|Gene_s=ADD1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:15773232
|Annotation=Ina study of 954 Chinese hypertensives, systolic blood pressure of those with ACE:I/D DD and ADD1:Gly460Trp Gly/Gly genotypes was significantly higher than carriers of ACE:I or ADD1:460Trp. However, genotype was not related to benazepril treatment response.
|Drugs=benazepril
|Drug Classes=
|Diseases=Hypertension
|Curation Level=Curated
|PharmGKB Accession ID=PA165107179
}}

{{PMID Auto
|PMID=20145305
|Title=Association between &amp;#945;-adducin gene polymorphism (Gly460Trp) and genetic predisposition to salt sensitivity: a meta-analysis
}}

{{PMID Auto
|PMID=19838659
|Title=alpha- and beta-Adducin polymorphisms affect podocyte proteins and proteinuria in rodents and decline of renal function in human IgA nephropathy
|OA=1
}}

{{PharmGKB
|RSID=rs4961
|Name_s=ADD1:Gly460Trp, rs4961 G>T, alpha-adducin Gly460Trp
|Gene_s=ADD1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:12623934
|Annotation=In a study of Italian hypertensives, patients carrying at least one I allele of ACE:I/D and one 460Trp allele (T variant) of alpha-adducin ADD1:Gly460Trp (rs4961 G>T) had the largest mean blood pressure decrease with hydrochlorothiazide treatment.
|Drugs=hydrochlorothiazide
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA165107177
}}

{{PMID Auto
|PMID=21291465
|Title=The association of genetic polymorphisms with cerebral palsy: a meta-analysis
}}

{{PMID Auto
|PMID=21339657
|Title=Angiotensin-converting enzyme (rs4646994) and ? ADDUCIN (rs4961) gene polymorphisms' study in primary spontaneous intracerebral hemorrhage
}}
{{omim
|id=102680
|rsnum=4961
|variant=0001
}}

{{ClinVar
|rsid=4961
|Reversed=0
|FwdREF=G
|FwdALT=T
|REF=G
|ALT=T
|RSPOS=2906707
|CHROM=4
|GMAF=0.2486
|dbSNPBuildID=52
|SSR=0
|SAO=1
|VP=0x05017800000015051f110101
|GENEINFO=ADD1:118
|GENE_NAME=ADD1
|GENE_ID=118
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000004.11:g.2906707G>T
|CLNORIGIN=1
|CLNSIG=255
|Tags=PM;TPA;PMC;SLO;VLD;G5;HD;GNO;KGPhase1;KGPilot123;KGPROD;OTHERKG;PH3;LSD;OM
|CAF=0.7511; 0.2489
|CLNACC=RCV000019936.1
|CLNDBN=Hypertension, salt-sensitive essential, susceptibility to
|CLNSRC=OMIM Allelic Variant
|CLNSRCID=102680.0001
|COMMON=1
|Disease=Hypertension
}}

{{PMID|18279468|OA=1
}} Ten renin-angiotensin system-related gene polymorphisms in maximally treated Canadian Caucasian patients with heart failure.

{{PMID|18398333|OA=1
}} Relationships among endogenous ouabain, alpha-adducin polymorphisms and renal sodium handling in primary hypertension.

{{PMID|18513389|OA=1
}} 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|OA=1
}} 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|OA=1
}} Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach.

{{PMID|19330901|OA=1
}} Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women's Genome Health Study.

{{PMID|19379518|OA=1
}} Development of a fingerprinting panel using medically relevant polymorphisms.

{{PMID|19559392|OA=1
}} A candidate gene association study of 77 polymorphisms in migraine.

{{PMID|19574959|OA=1
}} Novel genetic variants in the alpha-adducin and guanine nucleotide binding protein beta-polypeptide 3 genes and salt sensitivity of blood pressure.

{{PMID|20565774|OA=1
}} 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?

{{GET Evidence
|gene=ADD1
|aa_change=Gly460Trp
|aa_change_short=G460W
|impact=pathogenic
|qualified_impact=Insufficiently evaluated pathogenic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs4961
|overall_frequency_n=1686
|overall_frequency_d=10758
|overall_frequency=0.156721
|n_genomes=25
|n_genomes_annotated=0
|n_haplomes=28
|n_articles=3
|n_articles_annotated=3
|in_omim=Y
|in_pharmgkb=Y
|pph2_score=0.995
|nblosum100=7
|autoscore=3
|webscore=N
|summary_short=This variant is associated with salt-sensitivity in patients with hypertension.
}}

{{PMID Auto
|PMID=23122309
|Title=The relationship between polymorphisms at 17 gene sites and hypertension among the Aboriginal Tibetan people
}}

{{PMID Auto
|PMID=22810272
|Title=Computational study of ADD1 gene polymorphism associated with hypertension.
}}

{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | FTDNA}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}