Variant alleles of the D2 dopamine receptor gene and obesity
Variant alleles of the D2 dopamine receptor gene and obesity
复制标题
DOI：
10.1016/s0271-5317(00)00130-5
复制
发表时间：
2000-03-01
影响因子：
4.5
通讯作者：
Wu, XF
中科院分区：
文献类型：
--
作者：
Spitz, MR;Detry, MA;Wu, XF
中皮质边缘多巴胺能奖赏通路在食欲的神经调节中发挥作用。有数据支持 D2 多巴胺受体 (DRD2) 基因等位基因变体的作用以及受体结合位点的数量在药物滥用和肥胖易感性中的作用。我们最近证明 Al 和 B1 基因型处于连锁不平衡状态，可以预测吸烟状况。之前的研究评估了肥胖与 AI 之间的关系，但没有评估 B1 基因型。我们的目标是评估健康个体肥胖与 DRD2 TaqI A 和 TaqI B 基因型之间的关系。受试者为 139 名平均体重的白人和 37 名肥胖者（体重指数大于或等于 30），被确定为正在进行的病例对照研究的比较受试者。在肥胖组中，只有 41.7% 的人表现出 A2 基因型，58.3% 的人表现出 Al 基因型，而平均体重受试者的这一比例分别为 68.8% 和 31.2%（P=0.002）。 B2 基因型也有类似的模式（分别为 51.4% 和 78.9%，P=0.003）。与 DRD2 Al 基因型相关的肥胖风险为 3.48（95% 置信区间 = 1.55, 7.80），而 DRD2 B1 基因型的肥胖风险为 4.55（1.94, 10.69）。具有Al或BI基因型的个体比具有野生型基因型的个体具有更高的BMI（P分别=0.086和0.05）。 Al 基因型的患病率是：5 名从不吸烟的肥胖者中有 2 名（40%），22 名肥胖前吸烟者中有 12 名（54.6%），9 名肥胖当前吸烟者中有 7 名（77.9%）。 BI 基因型的可比百分比为 0%、56.5% 和 55.6%。需要进一步强调确定肥胖的遗传基础，以便制定有针对性的减肥干预措施，从而提高成功的可能性。 (C) 2000 爱思唯尔科学公司。
The mesocorticolimbic dopaminergic reward pathways have a role in the neuromodulation of appetite. There are data supporting a role of allelic variants of the D2 dopamine receptor (DRD2) gene and the number of receptor binding sites in vulnerability to substance abuse and obesity. We recently demonstrated that the Al and B1 genotypes are in linkage disequilibrium and predictive of smoking status. Previous studies have evaluated the relationship between obesity and AI but not B1 genotypes. Our objective was to assess the relationships between obesity and DRD2 TaqI A and TaqI B genotypes in healthy individuals. Subjects were 139 Caucasian average weight and 37 obese individuals (body mass index greater than or equal to 30) identified as comparison subjects for ongoing case-control studies. Among the obese group, only 41.7% exhibited the A2 genotypes and 58.3% the Al genotypes compared with 68.8% and 31.2% respectively for the average weight subjects (P=0.002). There was a similar pattern for B2 genotypes (51.4% compared with 78.9% respectively, P=0.003). The risk of obesity associated with the DRD2 Al genotypes was 3.48 (95% confidence intervals = 1.55, 7.80), compared with 4.55 (1.94, 10.69) for the DRD2 B1 genotypes. Individuals who had the Al or BI genotypes had higher BMI than those with the wildtype genotypes (P=0.086 and 0.05 respectively). The prevalence of the Al genotypes was' 2 of 5 (40%) obese individuals who never smoked, 12 of 22 (54.6%) for obese former smokers, and 7 of 9 (77.9%) for obese current smokers. The comparable percentages for the BI genotypes were 0%, 56.5% and 55.6%. Further emphasis needs to be placed on identifying the genetic basis for obesity in order to develop targeted weight reduction interventions, that may improve potential for success. (C) 2000 Elsevier Science Inc.