β-Arrestin 2 (ARRB2) Polymorphism is Associated With Adverse Consequences of Chronic Heroin Use.
β-Arrestin 2 (ARRB2) Polymorphism is Associated With Adverse Consequences of Chronic Heroin Use.
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DOI：
10.1111/ajad.13150
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发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Greenwald MK
中科院分区：
文献类型：
--
作者：
Karavidha KK;Burmeister M;Greenwald MK
β-arrestin 2是在G蛋白偶联受体活化期间募集的细胞内蛋白。在临床前研究中，β-抑制蛋白2与μ-阿片受体脱敏和内化以及阿片耐受性和依赖性的发展有关。本研究调查了阿片类药物使用障碍（OUD）个体中编码β-arrestin 2（ARRB 2）的基因变体与临床相关表型之间的关系。我们假设ARRB 2变异与长期使用海洛因的负面影响有关。长期海洛因使用者（N=201; n=103非裔美国人; n=98例白人）进行ARRB 2 r1045280基因分型（同义词，也影响转录因子GTF 2 IRD 1的结合基序）、rs 2036657（3 'UTR）和rs3786047（内含子），并评估上个月的使用频率、注射使用和海洛因使用的终生持续时间、海洛因戒断尝试的次数，和海洛因使用相关的后果。与TT基因型相比，非裔美国人ARRB 2 r1045280 C等位基因携带者终生使用海洛因的后果（特别是职业和健康相关）显着降低。在白种人组中没有显著的基因型差异。ARRB 2 rs 2036657与rs 1045280存在强连锁不平衡。这些结果与现有数据一致，说明了ARRB 2 r1045280中祖先依赖性等位基因变异对海洛因使用后果的作用。ARRB 2 r1045280 C等位基因在非洲裔参与者中发挥了保护作用。这些首次在人类中的发现，这应该是重复的，提供了支持的机制研究ARRB 2和相关的细胞内信号分子在OUD病因，治疗和复发预防。
β-arrestin 2 is an intracellular protein recruited during the activation of G-protein coupled receptors. In preclinical studies, β-arrestin 2 has been implicated in mu-opioid receptor desensitization and internalization and the development of opioid tolerance and dependence. The present study investigated relationships between variants in the gene encoding β-arrestin 2 (ARRB2) and clinically-relevant phenotypes among individuals with opioid use disorder (OUD). We hypothesized that ARRB2 variants would be associated with negative effects of long-term heroin use. Chronic heroin users (N=201; n=103 African American; n=98 Caucasian) were genotyped for ARRB2 r1045280 (synonymous, also affecting binding motif of transcription factor GTF2IRD1), rs2036657 (3’UTR) and rs3786047 (intron) and assessed for past-month frequency of use, injection use, and lifetime duration of heroin use, number of heroin quit-attempts, and heroin use-related consequences. Lifetime heroin-use consequences (especially occupational and health-related) were significantly lower for African American ARRB2 r1045280 C-allele carriers compared to the TT genotype. There was no significant genotype difference in the Caucasian group. ARRB2 rs2036657 was in strong linkage disequilibrium with rs1045280. These results, consistent with extant data, illustrate a role for ancestry-dependent allelic variation in ARRB2 r1045280 on heroin-use consequences. The ARRB2 r1045280 C-allele played a protective role in African-descent participants. These first-in-human findings, which should be replicated, provide support for mechanistic investigations of ARRB2 and related intracellular signaling molecules in OUD etiology, treatment and relapse prevention.
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影响因子：
3.3
作者：
Mori T;Kuzumaki N;Arima T;Narita M;Tateishi R;Kondo T;Hamada Y;Kuwata H;Kawata M;Yamazaki M;Sugita K;Matsuzawa A;Baba K;Yamauchi T;Higashiyama K;Nonaka M;Miyano K;Uezono Y;Narita M
通讯作者：
Narita M
影响因子：
4.8
作者：
Groer, Chad E.;Schmid, Cullen L.;Bohn, Laura M.
通讯作者：
Bohn, Laura M.
影响因子：
0.9
作者：
Ambrose-Lanci LM;Vaswani M;Clarke TK;Zeng A;Lohoff FW;Ferraro TN;Berrettini WH
通讯作者：
Berrettini WH
DOI：
10.1016/j.molbrainres.2003.11.009
发表时间：
2004-02-05
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Ferrer-Alcón, M;La Harpe, R;García-Sevilla, JA
通讯作者：
García-Sevilla, JA
通过反基因 RNA 下调 β-arrestin 2 增强吗啡镇痛并预防吗啡耐受
影响因子：
2.2
作者：
Bu, Huilian;Liu, Xijiang;Gao, Feng
通讯作者：
Gao, Feng