Weight-loss response to naltrexone/bupropion is modulated by the Taq1A genetic variant near DRD2 (rs1800497): A pilot study

Abstract

Naltrexone/bupropion (NB) is a US Food and Drug Administration-approved antiobesity medication. Clinical trials have shown variable weight loss, with responders and non-responders. NB is believed to act on central dopaminergic pathways to suppress appetite. The Taq1A polymorphism near DRD2 (rs1800497) is associated with the density of striatal dopamine D2 receptors, with individuals carrying the A allele (AA or AG; termed A1+) having 30%-40% fewer dopamine binding sites than those who do not carry the A allele (GG; termed A1-). We performed a pilot study to assess the association of the rs1800497 ANKK1 c.2137G > A (p.Glu713Lys) variant with weight loss with NB treatment in 33 subjects. Mean (SD) weight loss was 5.9% (3.2%) for the A1+ genotype group (n = 15) and 4.2% (4.2%) for the A1- genotype group (n = 18). The mean weight loss for the A1+ genotype group was significantly greater than the predefined clinically significant 4% weight-loss target (one-sample t-test, P = .035), whereas the mean weight loss for the A1- genotype group was not (P = .85). Individuals with the A1+ genotype appear to respond better to NB than A1- individuals.

Keywords: antiobesity drug; drug mechanism; obesity therapy; pharmacogenetics; weight control.

FIGURE 1

A, Weight-loss response of individual subjects with mean (SD) by genotype. B, Responders and non-responders by genotype at rs1800497 ANKK1 c.2137G > A (p.Glu713Lys) (A1 + is AA or AG; A1− is GG)