Westchester Medical Center, Valhalla, New York.
Columbia University Irving Medical Center, New York, New York.
Diabetes Obes Metab. 2021 Mar;23(3):850-853. doi: 10.1111/dom.14267. Epub 2021 Jan 8.
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.
纳曲酮/安非他酮 (NB) 是美国食品和药物管理局批准的一种抗肥胖药物。临床试验表明其具有不同程度的减重效果，存在应答者和无应答者。NB 被认为通过作用于中枢多巴胺能途径来抑制食欲。DRD2 基因 (rs1800497) 附近的 Taq1A 多态性与纹状体多巴胺 D2 受体的密度有关，携带 A 等位基因 (AA 或 AG; 称为 A1+) 的个体比不携带 A 等位基因 (GG; 称为 A1-) 的个体多巴胺结合位点少 30%-40%。我们进行了一项初步研究，评估了 rs1800497ANKK1 c.2137G > A (p.Glu713Lys) 变体与 33 名接受 NB 治疗的患者体重减轻之间的关系。A1+基因型组 (n = 15) 的平均 (SD) 体重减轻为 5.9% (3.2%)，A1-基因型组 (n = 18) 的平均体重减轻为 4.2% (4.2%)。A1+基因型组的平均体重减轻明显大于预先设定的 4%体重减轻目标 (单样本 t 检验，P = .035)，而 A1-基因型组的平均体重减轻则没有达到这一目标 (P = .85)。携带 A1+基因型的个体对 NB 的反应似乎优于 A1-个体。
