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).

rs5443

Parent Gene: HTR2A

Importance: 2
Less common allele: T = 49%
More common allele: C = 51%
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