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本文引用的文献

1
Association between the nociceptin receptor gene (OPRL1) single nucleotide polymorphisms and alcohol dependence.孤啡肽受体基因（OPRL1）单核苷酸多态性与酒精依赖之间的关联。
Addict Biol. 2008 Mar;13(1):88-94. doi: 10.1111/j.1369-1600.2007.00089.x.
2
Association analysis of genes encoding the nociceptin receptor (OPRL1) and its endogenous ligand (PNOC) with alcohol or illicit drug dependence.编码孤啡肽受体（OPRL1）及其内源性配体（PNOC）的基因与酒精或非法药物依赖的关联分析。
Addict Biol. 2008 Mar;13(1):80-7. doi: 10.1111/j.1369-1600.2007.00082.x. Epub 2007 Oct 2.
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GATA-1, -2 and -3 genes expression in bone marrow microenviroment with chronic aplastic anemia.
Hematology. 2007 Aug;12(4):331-5. doi: 10.1080/10245330701255288.
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The Interaction of Selection and Linkage. I. General Considerations; Heterotic Models.选择与连锁的相互作用。I. 一般考量；杂种优势模型。
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Lack of polymorphism in genes encoding mGluR 7, mGluR 8, GABA(A) receptor alfa-6 subunit and nociceptin/orphanin FQ receptor and panic disorder.编码代谢型谷氨酸受体7、代谢型谷氨酸受体8、γ-氨基丁酸A受体α-6亚基和孤啡肽/孤啡肽FQ受体的基因缺乏多态性与惊恐障碍
Psychiatr Genet. 2007 Feb;17(1):9. doi: 10.1097/YPG.0b013e32801118bc.
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Alcoholism and neuropeptides: an update.酒精中毒与神经肽：最新进展
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7
The Orphanin FQ / Nociceptin receptor as a novel drug target in psychiatric disorders.孤啡肽/痛敏肽受体作为精神疾病中的新型药物靶点。
CNS Neurol Disord Drug Targets. 2006 Apr;5(2):219-24. doi: 10.2174/187152706776359628.
8
Genetic influences on impulsivity, risk taking, stress responsivity and vulnerability to drug abuse and addiction.遗传对冲动性、冒险行为、应激反应以及药物滥用和成瘾易感性的影响。
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Pharmacogenetics and human molecular genetics of opiate and cocaine addictions and their treatments.阿片类药物和可卡因成瘾及其治疗的药物遗传学与人类分子遗传学
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痛敏肽/孤啡肽FQ受体基因OPRL1的两种变体与高加索人阿片类药物成瘾易感性相关的证据。

Evidence for association of two variants of the nociceptin/orphanin FQ receptor gene OPRL1 with vulnerability to develop opiate addiction in Caucasians.

作者信息

Briant Judith A, Nielsen David A, Proudnikov Dmitri, Londono Douglas, Ho Ann, Ott Jurg, Kreek Mary Jeanne

机构信息

Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York 10065, USA.

出版信息

Psychiatr Genet. 2010 Apr;20(2):65-72. doi: 10.1097/YPG.0b013e32833511f6.

DOI:10.1097/YPG.0b013e32833511f6
PMID:20032820
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3832186/
Abstract

OBJECTIVES

The OPRL1 gene encodes the nociceptin/orphanin FQ receptor, which plays a role in regulating tolerance and behavioral responses to morphine. However, there is limited information on whether variants of OPRL1 are associated with vulnerability to develop opiate addiction. In this study, we examined five variants of OPRL1 and their role in determining vulnerability to develop opiate addiction.

METHODS

We recruited 447 individuals: 271 former severe heroin addicts and 176 healthy controls. Using a 5'-fluorogenic exonuclease assay, we genotyped individuals at five variants in OPRL1. It was then determined whether there was a significant association of allele, genotype, or haplotype frequency with vulnerability to develop opiate addiction.

RESULTS

When the cohort was stratified by ethnicity, we found that, in Caucasians but not in African-Americans or Hispanics, the allele frequency of rs6090041 and rs6090043 were significantly associated point-wise with opiate addiction (P=0.03 and 0.04, respectively). Of the haplotypes formed by these two variants, one haplotype was found to be associated with protection from developing opiate addiction in both African-Americans (point-wise P=0.04) and Caucasians (point-wise P=0.04), and another haplotype with vulnerability to develop opiate addiction in Caucasians only (P=0.020).

CONCLUSION

This study provides evidence for an association of two variants of the OPRL1 gene, rs6090041 and rs6090043, with vulnerability to develop opiate addiction, suggesting a role for nociceptin/orphanin FQ receptor in the development of opiate addiction.

摘要

目的

OPRL1基因编码痛敏肽/孤啡肽FQ受体，该受体在调节对吗啡的耐受性和行为反应中起作用。然而，关于OPRL1基因变异是否与阿片类药物成瘾易感性相关的信息有限。在本研究中，我们检测了OPRL1基因的五个变异及其在确定阿片类药物成瘾易感性中的作用。

方法

我们招募了447名个体：271名曾经的重度海洛因成瘾者和176名健康对照者。使用5'-荧光外切酶分析，我们对个体的OPRL1基因的五个变异进行基因分型。然后确定等位基因、基因型或单倍型频率与阿片类药物成瘾易感性之间是否存在显著关联。

结果

当按种族对队列进行分层时，我们发现，在白种人中，而非非裔美国人或西班牙裔中，rs6090041和rs6090043的等位基因频率与阿片类药物成瘾呈显著的逐点关联（P值分别为0.03和0.04）。由这两个变异形成的单倍型中，一个单倍型在非裔美国人（逐点P=0.04）和白种人（逐点P=0.04）中均与预防阿片类药物成瘾相关，另一个单倍型仅在白种人中与阿片类药物成瘾易感性相关（P=0.020）。

结论

本研究为OPRL1基因的两个变异rs6090041和rs6090043与阿片类药物成瘾易感性之间的关联提供了证据，表明痛敏肽/孤啡肽FQ受体在阿片类药物成瘾的发生中起作用。