A phenome-wide association study of a lipoprotein-associated phospholipase A2 loss-of-function variant in 90 000 Chinese adults.

Background: Lipoprotein-associated phospholipase A (Lp-PLA) has been implicated in development of atherosclerosis; however, recent randomized trials of Lp-PLA inhibition reported no beneficial effects on vascular diseases. In East Asians, a loss-of-function variant in the PLA2G7 gene can be used to assess the effects of genetically determined lower Lp-PLA METHODS: PLA2G7 V279F (rs76863441) was genotyped in 91 428 individuals randomly selected from the China Kadoorie Biobank of 0.5 M participants recruited in 2004-08 from 10 regions of China, with 7 years' follow-up.

Occupancy of brain dopamine D3 receptors and drug craving: a translational approach.

Selective dopamine D(3) receptor (D(3)R) antagonists prevent reinstatement of drug-seeking behavior and decrease the rewarding effects of contextual cues associated with drug intake preclinically, suggesting that they may reduce drug craving in humans. GSK598809 is a selective D(3)R antagonist recently progressed in Phase I trials. The aim of this study was to establish a model, based on the determination of the occupancy of brain D(3)Rs (O(D(3))(R)) across species, to predict the ability of GSK598809 to reduce nicotine-seeking behavior in humans, here assessed as cigarette craving in smokers.