Center for Human Nutrition, David Geffen School of Medicine at UCLA, Los Angeles, California, USA; UCLA School of Nursing, Los Angeles, California, USA.
Obesity (Silver Spring). 2013 Sep;21(9):E467-73. doi: 10.1002/oby.20202. Epub 2013 May 13.
The brain reward circuits that promote drug abuse may also be involved in pleasure seeking behavior and food cravings observed in severely obese subjects. Drug addiction polymorphisms such as the TaqI A1 allele of the dopamine D2 receptor (DRD2) are associated with cocaine, alcohol, and opioid use, but few studies have linked DRD2 to food craving. Other genes such as the leptin receptor gene (LEPR) and mu-opioid receptor gene (OPRM1) that affect appetite and pleasure centers in the brain may also influence food addiction and obesity. The three genes together may function synergistically.
To evaluate associations between candidate genes, food craving, overeating, and BMI, we administered questionnaires including Power of Food Scale and Food Craving Inventory, conducted anthropometric measures, and collected blood from patients undergoing weight-loss treatment. Questionnaires and DNA specimens were collected for 80 participants.
Participants were mostly female (74%) and Caucasian (79%), with an average age of 53 years old. Mean BMI for all participants was 43 kg/m2 and was significantly associated in a linear fashion with Food Craving Inventory scores (P=0.0001) and Power of Food (P=0.02). The DRD2 TaqI A1 allele was significantly associated with BMI (P=0.04), while LEPR Lys109Arg and OPRM1 A118G variants were not. We stratified DRD2 by LEPR and OPRM1, and observed a significant interaction (P = 0.04) between DRD2 and LEPR, and a marginally significant interaction (P=0.06) between DRD2 and OPRM1.
Genes associated with addictive behavior and appetite control may therefore, in combination, markedly influence development of clinically severe obesity.
促进药物滥用的大脑奖励回路可能也与严重肥胖患者中观察到的寻求快感行为和食物渴望有关。多巴胺 D2 受体（DRD2）的 TaqI A1 等位基因等药物成瘾多态性与可卡因、酒精和阿片类药物的使用有关，但很少有研究将 DRD2 与食物渴望联系起来。其他基因，如影响大脑中食欲和愉悦中心的瘦素受体基因（LEPR）和μ-阿片受体基因（OPRM1），也可能影响食物成瘾和肥胖。这三个基因可能协同发挥作用。
为了评估候选基因、食物渴望、暴饮暴食和 BMI 之间的关联，我们对正在接受减肥治疗的患者进行了问卷调查，包括食物渴望量表和食物渴望量表，进行了人体测量学测量，并采集了血液。共收集了 80 名参与者的问卷和 DNA 样本。
参与者主要为女性（74%）和白种人（79%），平均年龄为 53 岁。所有参与者的平均 BMI 为 43kg/m2，与食物渴望量表评分呈线性相关（P=0.0001）和 Power of Food（P=0.02）。DRD2 TaqI A1 等位基因与 BMI 显著相关（P=0.04），而 LEPR Lys109Arg 和 OPRM1 A118G 变体则不相关。我们对 DRD2 进行了 LEPR 和 OPRM1 的分层，观察到 DRD2 和 LEPR 之间存在显著的相互作用（P=0.04），DRD2 和 OPRM1 之间存在边缘显著的相互作用（P=0.06）。
因此，与成瘾行为和食欲控制相关的基因可能共同显著影响临床严重肥胖的发展。
