TSPO polymorphism in individuals with alcohol use disorder: Association with cholesterol levels and withdrawal severity.
TSPO polymorphism in individuals with alcohol use disorder: Association with cholesterol levels and withdrawal severity.
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酒精使用障碍患者的 TSPO 多态性：与胆固醇水平和戒断严重程度的关联。
DOI：
10.1111/adb.12838
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发表时间：
2021
影响因子：
3.4
通讯作者：
Volkow,NoraD
中科院分区：
文献类型：
--
作者：
Wiers,CorindeE;MartinsDeCarvalho,Luana;Hodgkinson,ColinA;Schwandt,Melanie;Kim,SungWon;Diazgranados,Nancy;Wang,Gene-Jack;Goldman,David;Volkow,NoraD
转运蛋白（TSPO）将胆固醇转运到线粒体中，并参与类固醇生成。TSPO多态性rs6971影响胆固醇和其他TSPO配体的结合，包括正电子发射断层扫描（PET）成像放射性示踪剂。虽然人们认识到酒精会增加血浆高密度脂蛋白（HDL），但尚未评估其对总胆固醇和甘油三酯的影响沿着与TSPO基因型的关系。在这里，我们评估了酒精使用障碍（AUD）中血浆胆固醇和甘油三酯是否被破坏，以及它们与932名AUD参与者（DSM IV或5）和546名对照者中rs6971的相关性。与对照组相比，AUD参与者的血浆总胆固醇、HDL和甘油三酯水平显著较高，但低密度脂蛋白（LDL）水平不高。仅在AUD组中，TSPOr 6971对胆固醇、LDL和甘油三酯的血浆水平具有显著影响（AA（n = 62）> AG（n = 319）> GG（n = 551）），但对HDL水平没有影响。此外，我们发现TSPOrs 6971对戒断评分（临床研究所酒精戒断评估[CIWA]）有显著影响，AA（n = 50）的评分高于AG（n = 238）和GG（n = 428）。AUD参与者的CIWA评分与LDL呈负相关，与HDL呈正相关，但与总胆固醇或甘油三酯无关。这些发现证实了AUD中血浆胆固醇和HDL水平升高，并记录了甘油三酯显著升高。我们还首次揭示了AUD参与者中TSPOrs6971基因型与血浆胆固醇、LDL和甘油三酯水平（不包括HDL）以及戒断严重程度之间的相关性。中介分析显示，低密度脂蛋白（而不是高密度脂蛋白）影响之间的关联TSPO2和酒精戒断严重程度。
The translocator protein (TSPO) transports cholesterol into mitochondria and is involved in steroidogenesis. TheTSPOpolymorphism rs6971 influences binding of cholesterol and other TSPO ligands including positron‐emission tomography (PET) imaging radiotracers. Although it is recognized that alcohol increases plasma high‐density lipoproteins (HDLs), its effects on total cholesterol and triglycerides along with its relationship toTSPOgenotype have not been assessed. Here, we evaluated whether plasma cholesterol and triglycerides are disrupted in alcohol use disorder (AUD) and their association with rs6971 in 932 AUD participants (DSM IV or 5) and 546 controls. AUD participants compared with controls had significantly higher plasma levels of total cholesterol, HDL, and triglycerides, but not of low‐density lipoprotein (LDL). In the AUD group only,TSPOrs6971 had a significant effect on plasma levels of cholesterol, LDL, and triglycerides (AA (n = 62) > AG (n = 319) > GG (n = 551)), but not on HDL levels. Additionally, we showed a significant effect ofTSPOrs6971 on withdrawal scores (Clinical Institute Withdrawal Assessment for Alcohol [CIWA]), with higher scores in AA (n = 50) compared with AG (n = 238) and GG (n = 428). CIWA scores in AUD participants correlated negatively with LDL and positively with HDL, but not with total cholesterol or triglycerides. These findings corroborate elevated plasma cholesterol and HDL levels in AUD and document significant increases in triglycerides. We also reveal for the first time an association in AUD participants betweenTSPOrs6971 genotype and plasma cholesterol, LDL, and triglyceride levels (not for HDL) and with withdrawal severity. Mediation analyses revealed that LDL (but not HDL) influenced the association betweenTSPOand alcohol withdrawal severity.