rs5443 is a SNP in the HTR2A (GNB3) gene. It is associated with a number of metabolic conditions like obesity, diabetes, coronary heart diseases etc.
Mechanism
- This SNP codes for GNB3, which in turn codes for a second messenger complex associated with 5HT2A receptor signaling (R).
- The T allele is thought to increase secondary messenger signaling (R).
The T (minor) allele is associated with:
- Better response to viagra, more likely to be obese, hypertension, SSRI-induced sexual dysfunction, respond to triptans for migraines (TT). T allele carriers are 2-3 fold more likely to be obese in Caucasian, Chinese, and African American populations (R).
- Higher risk for hypertension (R).
- Significant weight gain during pregnancy (TT vs CT or CC). Women had a significantly higher pre-pregnancy body mass index (R).
- Better response to Viagra (TT). 91% of them have a "positive erectile response" upon taking Viagra, whereas only around 50% of CT and CC individuals respond equivalently to the drug (OR=10, p = 0.01) (R).
- Significant weight gain while taking anti-depressants. Patients with TT receiving clozapine over a long term for the treatment of schizophrenia gain significantly more weight (16%) compared to patients carrying at least one C allele in a study of Chinese patients (R).
- Better response to Triptans. T carriers taking triptans for the treatment of migraines or cluster headaches were ~3 fold more likely to respond positively compared with CC (OR 2.96, p=0.0074) in a study of ~200 Caucasian patients (R).
- Positively associated with endurance athletes [R]
The C (major) allele is associated with:
- GERD. CT genotypes are more prevalent in gastroesophageal reflux disease (GERD) patients relative to healthy controls (OR 1.43) (R).
- An inability to lose weight with the drug sibutramine. CC individuals do not lose weight under sibutramine (weight loss drug) therapy whereas CT and TT individuals do according to a study of 131 obese Taiwanese patients (R).