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From SNPedia

Geno Mag Summary
(C;C) 1.5 normal, but higher risk for several conditions
(C;T) 2.1 some risk
(T;T) 2.4 viagra is more likely to have an effect. increased metabolic disease risk.
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
1000 genomesrs5443
23andMe allrs5443
SNP Nexus

GWAS Ctlgrs5443
Max Magnitude2.4
? (C;C) (C;T) (T;T) 28
rs5443, a SNP in the G-protein beta3 subunit (GNB3) gene that is more commonly known as the C825T variant, has been linked to a number of metabolic conditions including obesity, coronary artery disease, insulin resistance and therefore diabetes, left ventricular hypertrophy, and hypertension. It has also been linked to how well a patient responds to Viagra (sildenafil). Several studies have been unable to replicate one or more of the associations in at least some populations between this SNP and these conditions. The more notable studies include:
  • rs5443(T) allele carriers are 2-3 fold more likely to be obese in Caucasian, Chinese, and African American populations. [PMID 10477144]
  • rs5443(T) carriers are clearly at higher risk for hypertension, but this review indicates that whether they are also at increased risk for stroke and left ventricular hypertrophy remains controversial. [PMID 12530935]
  • rs5443(T;T) women gain significantly more weight during pregnancy than rs5443(C;T) or rs5443(C;C) women, and had a significantly higher pre-pregnancy body mass index. [PMID 12668921]
  • rs5443(T;T) genotypes respond to Viagra better. 91% of them have a "positive erectile response" upon taking Viagra, whereas only around 50% of rs5443(C;T) and rs5443(C;C) individuals respond equivalently to the drug. The odds ratio for the positive response was 10.0 (CI: 1.2 - 81.1, p = 0.01). [PMID 12576843]
  • rs5443(T;T) patients receiving clozapine over a long term for the treatment of schizophrenia gain significantly more weight (16%) compared to patients carrying at least one rs5443(C) allele in a study of Chinese patients. [PMID 16141801]
  • rs5443(T) carriers taking triptans for the treatment of migraines or cluster headaches were ~3 fold more likely to respond positively compared with rs5443(C;C) homozygotes (OR 2.96, CI:1.34 - 6.56, p=0.0074) in a study of ~200 Caucasian patients. [PMID 17361120]
  • rs5443(C;T) genotypes are more prevalent in gastroesophageal reflux disease (GERD) patients relative to healthy controls (odds ratio 1.43, CI: 1.04–1.98).[PMID 19174793]
  • rs5443(C;C) individuals do not lose weight under sibutramine therapy whereas (C;T) and (T;T) individuals do, based on a study of 131 obese Taiwanese patients.[PMID 19687782] 23andMe blog

[PMID 19560507] Interaction of serotonin-related genes affects short-term antidepressant response in major depressive disorder

[PMID 19772422] Common Variants in the G Protein beta3 Subunit Gene and Thyroid Disorders in a Formerly Iodine-Deficient Population

[PMID 19811352] Lack of an association of GNB3 C825T polymorphism and blood pressure in patients with rheumatoid arthritis

[PMID 21371559] Effects of C825T polymorphism of the GNB3 gene on availability of dopamine transporter in healthy volunteers-a SPECT study

[PMID 21675276] [A protective effect of GLY272SER polymorphism of GNB3 gene in development of essential hypertension and its relations with environmental hypertension risk factors]

[PMID 22041889] Improvement of non-steroidal anti-inflammatory drug-induced gastrointestinal symptoms during proton pump inhibitor treatment: Are g-protein (beta)3 subunit genotype, helicobacter pylori status, and environmental factors response modifiers?

[PMID 22791279OA-icon.png] Association of the C825T polymorphism in the GNB3 gene with obesity and metabolic phenotypes in a Taiwanese population

[PMID 17521439OA-icon.png] Association between 5-HT2A, TPH1 and GNB3 genotypes and response to typical neuroleptics: a serotonergic approach.

[PMID 18248681OA-icon.png] Prevalence of common disease-associated variants in Asian Indians.

[PMID 18304332OA-icon.png] No evidence for association between BMI and 10 candidate genes at ages 4, 7 and 10 in a large UK sample of twins.

[PMID 18308786] The --1019 C/G polymorphism of the 5-HT(1)A receptor gene is associated with negative symptom response to risperidone treatment in schizophrenia patients.

[PMID 18513389OA-icon.png] New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.

[PMID 18656447] Salt consumption-dependent association of the GNB3 gene polymorphism with type 2 DM.

[PMID 19131662OA-icon.png] A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients.

[PMID 19263529OA-icon.png] Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach.

[PMID 19303909] Intensity of opiate withdrawal in relation to the 825C>T polymorphism of the G-protein beta 3 subunit gene.

[PMID 19330901OA-icon.png] Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women's Genome Health Study.

[PMID 19360113OA-icon.png] The Role of the PGC1alpha Gly482Ser Polymorphism in Weight Gain due to Intensive Diabetes Therapy.

[PMID 19559392OA-icon.png] A candidate gene association study of 77 polymorphisms in migraine.

[PMID 19885780] GNB3 C825T polymorphism and elevated blood pressure.

[PMID 20021678OA-icon.png] Evaluation of self-reported ethnicity in a case-control population: the stroke prevention in young women study.

[PMID 20359253] Effect of the common -866G/A polymorphism of the uncoupling protein 2 gene on weight loss and body composition under sibutramine therapy in an obese Taiwanese population.

[PMID 20386734OA-icon.png] Further evidence supporting a role for gs signal transduction in severe malaria pathogenesis.

[PMID 21172166OA-icon.png] Pharmacogenetics of antidepressant response.

[PMID 21210858] Is there an interaction between BDKRB2 -9/+9 and GNB3 C825T polymorphisms and elite athletic performance?

[PMID 21735268] [Genotype of the GNB3 C825T polymorphism, A risk factor for the development and course of prostate cancer?].

[PMID 21737952] Genetic variation in gsalpha protein as a new indicator in screening test for vasovagal syncope.

GET Evidence
impact pharmacogenetic
qualified_impact Insufficiently evaluated pharmacogenetic
overall_frequency 0.453802

[PMID 22534794] A two-stage matched case-control study on multiple hypertensive candidate genes in Han Chinese.

[PMID 23339167] Single nucleotide polymorphisms in G protein signaling pathway genes in preeclampsia.

[PMID 23733030] Pharmacogenetics in major depression: a comprehensive meta-analysis.

[PMID 26083990] Influence of P2Y12 polymorphisms on platelet activity but not ex-vivo antiplatelet effect of ticagrelor in healthy Chinese male subjects

[PMID 27660894] Association of CLOCK, ARNTL, PER2, and GNB3 polymorphisms with diurnal preference in a Korean population.

Risk rs5443(T;T)
Alt rs5443(T;T)
Reference rs5443(C;C)
Significance Drug-response
Disease sildenafil response - Efficacy
Variation info
Gene GNB3
CLNDBN sildenafil response - Efficacy
Reversed 0
HGVS NC_000012.11:g.6954875C>T
CLNSRC PharmGKB Clinical Annotation PharmGKB
CLNACC RCV000211272.1,