Rs5443

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] spittoon

[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?