Evidence map›Paper›PMID 25122903›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014

A heroin addiction severity-associated intronic single nucleotide polymorphism modulates alternative pre-mRNA splicing of the μ opioid receptor gene OPRM1 via hnRNPH interactions.

Jin Xu, Zhigang Lu, Mingming Xu, Ling Pan, Yi Deng, Xiaohu Xie, Huifen Liu, Shixiong Ding, Yasmin L Hurd, Gavril W Pasternak and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
8.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Biochemical Diagnosis in Substance and Non-substance Addiction.Advances in experimental medicine and biology · 2025
    Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Hnrnph1 is a novel regulator of alcohol reward.Drug and alcohol dependence · 2021
    Article
  19. Review
  20. Opioid and neuroHIV Comorbidity - Current and Future Perspectives.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Jin XuDepartment of Neurology and the Molecular Pharmacology & Chemistry Program, and.
Zhigang LuDepartment of Neurology and the Molecular Pharmacology & Chemistry Program, and.
Mingming XuDepartment of Neurology and the Molecular Pharmacology & Chemistry Program, and.
Ling PanDepartment of Neurology and the Molecular Pharmacology & Chemistry Program, and.
Yi DengDepartment of Neurology and the Molecular Pharmacology & Chemistry Program, and.
Xiaohu XieLaboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, People's Republic of China.
Huifen LiuLaboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, People's Republic of China.
Shixiong DingLaboratory of Clinical Biochemistry, Ningbo No. 2 Hospital, Zhejiang 315100, People's Republic of China.
Yasmin L HurdDepartments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029, and.
Gavril W PasternakDepartment of Neurology and the Molecular Pharmacology & Chemistry Program, and.ORCID http://orcid.org/0000-0003-0060-6996
Robert J KleinDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065.ORCID http://orcid.org/0000-0003-3539-5391
Luca CartegniSusan Lehman Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854.
Wenhua ZhouLaboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, People's Republic of China, pany@mskcc.org whzhou@vip.163.com.ORCID http://orcid.org/0000-0002-4804-7559
Ying-Xian PanDepartment of Neurology and the Molecular Pharmacology & Chemistry Program, and pany@mskcc.org whzhou@vip.163.com.
Memorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
TRAINING IN BEHAV. PHARMACOLOGY OF HUMAN DRUG DEPENDENCET32DA007242 · NIDA · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI HEIL, SARAH H, HIGGINS, STEPHEN T · 1990 to 2025
$8.2M
The Opioid mesolimbic system in heroin abuseR01DA015446 · NIDA · KAROLINSKA INSTITUTE · PI HURD, YASMIN L. · 2002 to 2018
$7.1M
Synthesis &Pharmacology of Novel Opiates and SystemsR01DA006241 · NIDA · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PAN, YING-XIAN · 1990 to 2018
$6.4M
PHARMACOLOGY OF OPIOID RECEPTOR SUBTYPESR01DA007242 · NIDA · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PAN, YING-XIAN · 1991 to 2022
$6.0M
Characterizing exon 11 promoter of the mu opioid receptor gene, OPRMR01DA013997 · NIDA · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PAN, YING-XIAN · 2002 to 2012
$3.3M
Linking disease-associated variants to transcriptional regulation using ENCODEU01HG007033 · NHGRI · SLOAN-KETTERING INST CAN RESEARCH · PI KLEIN, ROBERT J. · 2012 to 2015
$1.9M
PHARMACOLOGY OF OPIOID RECEPTOR SUBTYPESR37DA007242 · NIDA · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PASTERNAK, GAVRIL W · 1996 to 2004
$1.5M
Biochemical Characterization of Opioid BInding SitesR56DA002615 · NIDA · SLOAN-KETTERING INST CAN RESEARCH · PI PASTERNAK, GAVRIL W · 2012 to 2013
$1.1M
Molecular Neurobiology of Human Drug AbuseR56DA015446 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HURD, YASMIN L. · 2019 to 2019
$564k
Exploring functions of mu opioid receptor carboxyl termini by gene targetingR21DA029244 · NIDA · SLOAN-KETTERING INST CAN RESEARCH · PI PAN, YING-XIAN · 2010 to 2011
$522k
NCI NIH HHS CA08748NCI NIH HHS P30 CA008748NHGRI NIH HHS U01 HG007033NIDA NIH HHS DA013997NIDA NIH HHS DA015446NIDA NIH HHS DA02944NIDA NIH HHS DA06241NIDA NIH HHS DA07242NIDA NIH HHS R01 DA006241NIDA NIH HHS R01 DA007242NIDA NIH HHS R01 DA013997NIDA NIH HHS R01 DA015446NIDA NIH HHS R21 DA029244NIDA NIH HHS R37 DA007242NIDA NIH HHS R56 DA002615NIDA NIH HHS R56 DA015446NIDA NIH HHS T32 DA007242
6 · The paper itself

Abstract

Single nucleotide polymorphisms (SNPs) in the OPRM1 gene have been associated with vulnerability to opioid dependence. The current study identifies an association of an intronic SNP (rs9479757) with the severity of heroin addiction among Han-Chinese male heroin addicts. Individual SNP analysis and haplotype-based analysis with additional SNPs in the OPRM1 locus showed that mild heroin addiction was associated with the AG genotype, whereas severe heroin addiction was associated with the GG genotype. In vitro studies such as electrophoretic mobility shift assay, minigene, siRNA, and antisense morpholino oligonucleotide studies have identified heterogeneous nuclear ribonucleoprotein H (hnRNPH) as the major binding partner for the G-containing SNP site. The G-to-A transition weakens hnRNPH binding and facilitates exon 2 skipping, leading to altered expressions of OPRM1 splice-variant mRNAs and hMOR-1 proteins. Similar changes in splicing and hMOR-1 proteins were observed in human postmortem prefrontal cortex with the AG genotype of this SNP when compared with the GG genotype. Interestingly, the altered splicing led to an increase in hMOR-1 protein levels despite decreased hMOR-1 mRNA levels, which is likely contributed by a concurrent increase in single transmembrane domain variants that have a chaperone-like function on MOR-1 protein stability. Our studies delineate the role of this SNP as a modifier of OPRM1 alternative splicing via hnRNPH interactions, and suggest a functional link between an SNP-containing splicing modifier and the severity of heroin addiction.

Indexed as

IntronsPolymorphism, Single NucleotideRNA SplicingAllelesGene FrequencyGenetic Predisposition to DiseaseGenotypeHaplotypesHeroin DependenceHeterogeneous-Nuclear Ribonucleoprotein Group F-HHumansLinkage DisequilibriumMaleReceptors, Opioid, muSeverity of Illness IndexHeterogeneous-Nuclear Ribonucleoprotein Group F-HOPRM1 protein, humanReceptors, Opioid, muaddictionheroinhnRNPHopioid receptorSNPsplicing

Identifiers

PMID25122903
PMCPMC4131016
OpenAlexW2071140375

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.