{{Rsnum
|rsid=5443
|Gene=GNB3
|Chromosome=12
|position=6845711
|Orientation=plus
|ReferenceAllele=C
|GMAF=0.4775
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
|Gene_s=GNB3
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 34.9 | 55.6 | 9.5
| HCB | 40.0 | 51.1 | 8.9
| JPT | 38.6 | 43.2 | 18.2
| YRI | 1.6 | 14.5 | 83.9
| ASW | 0.0 | 0.0 | 0.0
| CHB | 40.0 | 51.1 | 8.9
| CHD | 0.0 | 0.0 | 0.0
| GIH | 0.0 | 0.0 | 0.0
| LWK | 0.0 | 0.0 | 0.0
| MEX | 0.0 | 0.0 | 0.0
| MKK | 0.0 | 0.0 | 0.0
| TSI | 0.0 | 0.0 | 0.0
| HapMapRevision=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}} [http://blog.23andme.com/2008/10/16/snpwatch-genetic-variants-affect-weight-loss-drug-effectiveness/ 23andMe blog]

{{PMID Auto
|PMID=19560507
|Title=Interaction of serotonin-related genes affects short-term antidepressant response in major depressive disorder
}}
{{PMID Auto
|PMID=19772422
|Title=Common Variants in the G Protein beta3 Subunit Gene and Thyroid Disorders in a Formerly Iodine-Deficient Population
}}
{{PMID Auto
|PMID=19811352
|Title=Lack of an association of GNB3 C825T polymorphism and blood pressure in patients with rheumatoid arthritis
}}

{{PharmGKB
|RSID=rs5443
|Name_s=
|Gene_s=GNB3, USP5
|Feature=Exon/Syn, Intron
|Evidence=PubMed ID:19247266
|Annotation=Risk or phenotype-associated allele: T. Phenotype: Among GNB3 T allele carriers, the risk of diabetes due to thiazide use was less increased than among homozygous GNB3 CC subjects . Study size: 497 incident cases of type 2 diabetes and 2,633 controls. metric(s): (SI 0.62 (95% CI: 0.41-0.93). Type of association: GN.
|Drugs=
|Drug Classes=THIAZIDE DERIVATIVES
|Diseases=Diabetes Mellitus, Type 2
|Curation Level=Curated
|PharmGKB Accession ID=PA165109228
}}

{{PharmGKB
|RSID=rs5443
|Name_s=GNB3:825C>T; GNB3:Ser275Ser
|Gene_s=GNB3, USP5
|Feature=Exon/Syn, Intron
|Evidence=PubMed ID:1600156; PubMed ID:16707857; PubMed ID:17278960; PubMed ID:17663734; PubMed ID:17701674; PubMed ID:17785925
|Annotation=Extensively studied, found to be associated with many things, including blood pressure and hypertension.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA161145077
}}

{{PharmGKB
|RSID=rs5443
|Name_s=GNB3:825C>T; GNB3:Ser275Ser
|Gene_s=GNB3, USP5
|Feature=Exon/Syn, Intron
|Evidence=PubMed ID:12576843
|Annotation=This variant is associated with sildenafil response for erectile dysfunction patients.
|Drugs=sildenafil
|Drug Classes=
|Diseases=Erectile Dysfunction
|Curation Level=Curated
|PharmGKB Accession ID=PA161822201
}}

{{PharmGKB
|RSID=rs5443
|Name_s=GNB3:825C>T; GNB3:Ser275Ser
|Gene_s=GNB3, USP5
|Feature=Exon/Syn, Intron
|Evidence=PubMed ID:18551043
|Annotation=This variant is associated with statin response. Patients carring T allele have less risk of MI and are more likely to benefit from statin therapy in a hypercholesterolemic population of antihypertensive drug users.
|Drugs=atorvastatin; fluvastatin; lovastatin; pravastatin; rosuvastatin; simvastatin
|Drug Classes=HMG COA REDUCTASE INHIBITORS
|Diseases=Hypercholesterolemia
|Curation Level=Curated
|PharmGKB Accession ID=PA161845790
}}

{{PharmGKB
|RSID=rs5443
|Name_s=GNB3:825C>T; GNB3:Ser275Ser
|Gene_s=GNB3, USP5
|Feature=Exon/Syn, Intron
|Evidence=PubMed ID:17136758
|Annotation=This variant (C allele carriers) is associated with an increased risk for the development of oncocytic thyroid tumours.
|Drugs=
|Drug Classes=
|Diseases=Thyroid Neoplasms
|Curation Level=Curated
|PharmGKB Accession ID=PA161845791
}}

{{PharmGKB
|RSID=rs5443
|Name_s=GNB3:825C>T; GNB3:Ser275Ser
|Gene_s=GNB3, USP5
|Feature=Exon/Syn, Intron
|Evidence=PubMed ID:17361120
|Annotation=A study on A total of 180 migraine and cluster headache patients found that pain relief by triptans is significantly modulated by this common genetic GNB3 variant.
|Drugs=almotriptan
|Drug Classes=
|Diseases=Migraine without Aura
|Curation Level=Curated
|PharmGKB Accession ID=PA162263548
}}

{{PharmGKB
|RSID=rs5443
|Name_s=GNB3:825C>T; GNB3:Ser275Ser
|Gene_s=GNB3, USP5
|Feature=Exon/Syn, Intron
|Evidence=PubMed ID:17361120
|Annotation=A study on a total of 180 migraine and cluster headache patients found that pain relief by triptans is significantly modulated by this common genetic GNB3 variant.
|Drugs=almotriptan; eletriptan; naratriptan; rizatriptan; sumatriptan; zolmitriptan
|Drug Classes=
|Diseases=Migraine without Aura
|Curation Level=Curated
|PharmGKB Accession ID=PA162364006
}}

{{PharmGKB
|RSID=rs5443
|Name_s=GNB3:825C>T
|Gene_s=GNB3, USP5
|Feature=Exon/Syn, Intron
|Evidence=PubMed ID:19193342
|Annotation=T allele is associated with olanzapine-induced weight gain
|Drugs=olanzapine
|Drug Classes=
|Diseases=Weight gain
|Curation Level=Curated
|PharmGKB Accession ID=PA164889042
}}

{{PMID Auto
|PMID=21371559
|Title=Effects of C825T polymorphism of the GNB3 gene on availability of dopamine transporter in healthy volunteers-a SPECT study
}}

{{PMID Auto
|PMID=21675276
|Title=[A protective effect of GLY272SER polymorphism of GNB3 gene in development of essential hypertension and its relations with environmental hypertension risk factors]
}}

{{PMID Auto
|PMID=22041889
|Title=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 Auto
|PMID=22791279
|Title=Association of the C825T polymorphism in the GNB3 gene with obesity and metabolic phenotypes in a Taiwanese population
|OA=1
}}

{{PMID Auto
|PMID=17521439
|Title=Association between 5-HT2A, TPH1 and GNB3 genotypes and response to typical neuroleptics: a serotonergic approach.
|OA=1
}}

{{PMID Auto
|PMID=18248681
|Title=Prevalence of common disease-associated variants in Asian Indians.
|OA=1
}}

{{PMID Auto
|PMID=18304332
|Title=No evidence for association between BMI and 10 candidate genes at ages 4, 7 and 10 in a large UK sample of twins.
|OA=1
}}

{{PMID Auto
|PMID=18308786
|Title=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 Auto
|PMID=18513389
|Title=New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.
|OA=1
}}

{{PMID Auto
|PMID=18656447
|Title=Salt consumption-dependent association of the GNB3 gene polymorphism with type 2 DM.
}}

{{PMID Auto
|PMID=19131662
|Title=A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients.
|OA=1
}}

{{PMID Auto
|PMID=19263529
|Title=Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach.
|OA=1
}}

{{PMID Auto
|PMID=19303909
|Title=Intensity of opiate withdrawal in relation to the 825C>T polymorphism of the G-protein beta 3 subunit gene.
}}

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

{{PMID Auto
|PMID=19360113
|Title=The Role of the PGC1alpha Gly482Ser Polymorphism in Weight Gain due to Intensive Diabetes Therapy.
|OA=1
}}

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

{{PMID Auto
|PMID=19885780
|Title=GNB3 C825T polymorphism and elevated blood pressure.
}}

{{PMID Auto
|PMID=20021678
|Title=Evaluation of self-reported ethnicity in a case-control population: the stroke prevention in young women study.
|OA=1
}}

{{PMID Auto
|PMID=20359253
|Title=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 Auto
|PMID=20386734
|Title=Further evidence supporting a role for gs signal transduction in severe malaria pathogenesis.
|OA=1
}}

{{PMID Auto
|PMID=21172166
|Title=Pharmacogenetics of antidepressant response.
|OA=1
}}

{{PMID Auto
|PMID=21210858
|Title=Is there an interaction between BDKRB2 -9/+9 and GNB3 C825T polymorphisms and elite athletic performance?
}}

{{PMID Auto
|PMID=21735268
|Title=[Genotype of the GNB3 C825T polymorphism, A risk factor for the development and course of prostate cancer?].
}}

{{PMID Auto
|PMID=21737952
|Title=Genetic variation in gsalpha protein as a new indicator in screening test for vasovagal syncope.
}}

{{GET Evidence
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs5443
|overall_frequency_n=4882
|overall_frequency_d=10758
|overall_frequency=0.453802
|n_genomes=37
|n_genomes_annotated=0
|n_haplomes=52
|n_articles=2
|n_articles_annotated=0
|in_pharmgkb=Y
|autoscore=1
|webscore=N
}}

{{PMID Auto
|PMID=22534794
|Title=A two-stage matched case-control study on multiple hypertensive candidate genes in Han Chinese.
}}

{{PMID Auto
|PMID=23339167
|Title=Single nucleotide polymorphisms in G protein signaling pathway genes in preeclampsia.
}}

{{PMID Auto
|PMID=23733030
|Title=Pharmacogenetics in major depression: a comprehensive meta-analysis.
}}

{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | HumanOmni1Quad}}