Article
Evidence for the contribution of genetic variations in regulator of G protein signaling 9 to the genetic susceptibility of heroin dependence
- Authors:
- Yongsheng Zhu
- Hongbo Zhang
-
View Affiliations / Copyright
Affiliations:
College of Forensic Science, Xi'an Jiaotong University, Key Laboratory of Ministry of Public Health for Forensic Science, Xi'an, Shaanxi 710061, P.R. China
-
Pages:
3908-3913
|
Published online on:
January 16, 2015
https://doi.org/10.3892/mmr.2015.3210
- Expand metrics +
Metrics:
Total
Views: 0
(Spandidos Publications: | PMC Statistics:
)
Metrics:
Total PDF Downloads: 0
(Spandidos Publications: | PMC Statistics:
)
This article is mentioned in:
Abstract
Regulator of G protein signaling (RGS) proteins are responsible for the rapid turnoff of G protein-coupled receptor signaling pathways. RGS9‑2, a brain‑specific splice variant of the RGS9 gene, is highly expressed in the striatum but lowly expressed in the periaqueductal gray and spinal cord, which mediate various actions of morphine and other opiates. In order to identify the markers that contribute to the genetic susceptibility of heroin dependence, the potential association between heroin dependence and 10 single nucleotide polymorphisms (SNPs), including rs8077696, rs8070231, rs2292593, rs2292592, rs9916525, rs1122079, rs4790953, rs1530351, rs4791230 and rs2869577 of the RGS9 gene was evaluated using the MassARRAY system. The present study recruited 425 heroin‑dependent patients and 205 healthy controls. The results revealed that two SNPs (rs1530351 and rs4791230) located in the promoter region of the RGS9 gene, were significantly associated with heroin dependence (P<0.05). The frequency of the C allele in rs1530351 (χ2=8.031, P=0.005, OR=2.079, 95% CI=1.241‑3.483) and the G allele in rs4791230 (χ2=7.360, P=0.007, OR=2.021, 95% CI=1.205‑3.389) in the heroin‑dependent patients was significantly higher than that in the controls. Furthermore, linkage disequilibrium was observed in three blocks (D'>0.9) and significantly less T‑A haplotypes (χ2=4.867, P=0.027, OR=0.442, 95% CI=0.210‑0.929) were identified in the heroin‑dependent patients, suggesting that they may exhibit protective effects against heroin dependence. These findings indicate a role for RGS9 gene polymorphisms in heroin dependence and may be informative for future genetic or biological studies on heroin dependence.
View References
|
1
|
Koob GF: The neurobiology of addiction: a
neuroadaptational view relevant for diagnosis. Addiction. 101(Suppl
1): 23–30. 2006. View Article : Google Scholar : PubMed/NCBI
|
|
2
|
Kreek MJ, Nielsen DA, Butelman ER and
LaForge KS: Genetic influences on impulsivity, risk taking, stress
responsivity and vulnerability to drug abuse and addiction. Nat
Neurosci. 8:1450–1457. 2005. View
Article : Google Scholar : PubMed/NCBI
|
|
3
|
Cadoret RJ, Yates WR, Troughton E,
Woodworth G and Stewart MA: Adoption study demonstrating two
genetic pathways to drug abuse. Arch Gen Psychiatry. 52:42–52.
1995. View Article : Google Scholar : PubMed/NCBI
|
|
4
|
Uhl GR: Molecular genetics of substance
abuse vulnerability: remarkable recent convergence of genome scan
results. Ann NY Acad Sci. 1025:1–13. 2004. View Article : Google Scholar : PubMed/NCBI
|
|
5
|
Uhl GR, Drgon T, Johnson C, et al: ‘Higher
order’ addiction molecular genetics: convergent data from
genome-wide association in humans and mice. Biochem Pharmacol.
75:98–111. 2008. View Article : Google Scholar
|
|
6
|
Zachariou V, Georgescu D, Sanchez N, et
al: Essential role for RGS9 in opiate action. Proc Nal Acad Sci
USA. 100:13656–13661. 2003. View Article : Google Scholar
|
|
7
|
Badgaiyan RD: A novel perspective on
dopaminergic processing of human addiction. J Alcohol Drug Depend.
1:1000e1012013.PubMed/NCBI
|
|
8
|
Volkow ND, Fowler JS, Wang GJ, Swanson JM
and Telang F: Dopamine in drug abuse and addiction: results of
imaging studies and treatment implications. Arch Neurol.
64:1575–1579. 2007. View Article : Google Scholar : PubMed/NCBI
|
|
9
|
Dohlman HG and Thorner J: RGS proteins and
signaling by heterotrimeric G proteins. J Biol Chem. 272:3871–3874.
1997. View Article : Google Scholar : PubMed/NCBI
|
|
10
|
Rahman Z, Gold SJ, Potenza MN, et al:
Cloning and characterization of RGS9-2: a striatal-enriched
alternatively spliced product of the RGS9 gene. J Neurosci.
19:2016–2026. 1999.PubMed/NCBI
|
|
11
|
Birnbaumer L: Expansion of signal
transduction by G proteins. The second 15 years or so: from 3 to 16
alpha subunits plus betagamma dimers. Biochim Biophys Acta.
1768:772–793. 2007. View Article : Google Scholar : PubMed/NCBI
|
|
12
|
Traynor JR and Neubig RR: Regulators of G
protein signaling and drugs of abuse. Mol Interv. 5:30–41. 2005.
View Article : Google Scholar : PubMed/NCBI
|
|
13
|
Hooks SB, Martemyanov K and Zachariou V: A
role of RGS proteins in drug addiction. Biochem Pharmacol.
75:76–84. 2008. View Article : Google Scholar
|
|
14
|
Traynor JR, Terzi D, Caldarone BJ and
Zachariou V: RGS9-2: probing an intracellular modulator of behavior
as a drug target. Trends Pharmacol Sci. 30:105–111. 2009.
View Article : Google Scholar : PubMed/NCBI
|
|
15
|
Zhang K, Howes KA, He W, et al: Structure,
alternative splicing and expression of the human RGS9 gene. Gene.
240:23–34. 1999. View Article : Google Scholar : PubMed/NCBI
|
|
16
|
Escamilla M, Hare E, Dassori AM, et al: A
schizophrenia gene locus on chromosome 17q21 in a new set of
families of Mexican and central american ancestry: evidence from
the NIMH genetics of schizophrenia in latino populations study. Am
J Psychiatry. 166:442–449. 2009. View Article : Google Scholar : PubMed/NCBI
|
|
17
|
Greenbaum L, Pelov I, Teltsh O, Lerer B
and Kohn Y: No association between regulator of G-protein signaling
9 (RGS9) and schizophrenia in a Jewish population. Psychiatr Genet.
20:47–48. 2010. View Article : Google Scholar
|
|
18
|
Clarke GM, Anderson CA, Pettersson FH,
Cardon LR, Morris AP and Zondervan KT: Basic statistical analysis
in genetic case-control studies. Nat Protoc. 6:121–133. 2011.
View Article : Google Scholar : PubMed/NCBI
|
|
19
|
Rousset F and Raymond M: Testing
heterozygote excess and deficiency. Genetics. 140:1413–1419.
1995.PubMed/NCBI
|
|
20
|
Anderson GR, Posokhova E and Martemyanov
KA: The R7 RGS protein family: multi-subunit regulators of neuronal
G protein signaling. Cell Biochem Biophys. 54:33–46. 2009.
View Article : Google Scholar : PubMed/NCBI
|
|
21
|
Zhou Y, Shi T, Mozola MA, et al: Evidence
that the promoter can influence assembly of antitermination
complexes at downstream RNA sites. J Bacteriol. 188:2222–2232.
2006. View Article : Google Scholar : PubMed/NCBI
|
