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.


 * 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.


 * 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.


 * 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).


 * 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.


 * 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.


 * rs5443(C;T) genotypes are more prevalent in gastroesophageal reflux disease (GERD) patients relative to healthy controls (odds ratio 1.43, CI: 1.04&#8211;1.98).


 * 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. 23andMe blog