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BMC Psychiatry
Published in: BMC Psychiatry 1/2013

Open Access 01-12-2013 | Research article

Association study of OPRM1 polymorphisms with Schizophrenia in Han Chinese population

Authors: Saidan Ding, Bicheng Chen, Yong Zheng, Qin Lu, Leping Liu, Qǐ-Chuan Zhuge

Published in: BMC Psychiatry | Issue 1/2013

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Abstract

Background

The expression of μ-opioid receptor has important role in cognitive dysfunction in Schizophrenia (SZ). The results of studies about the association of polymorphisms of μ-opioid receptor gene (OPRM1) with SZ were inconsistent.

Methods

We conducted a case–control study to investigate the genetic association between OPRM1 polymorphisms and SZ among the Han chinese population. 264 SZ patients and 264 age-matched control subjects were recruited. Four SNPs of OPRM1 were successfully genotyped by using PCR-RFLP.

Results

Of four polymorphisms, rs1799971 and rs2075572 were shown to associate with SZ. Compared with the A allele of rs1799971 and C allele of rs2075572, the G allele of rs1799971 and rs2075572 was associated with an almost 0.46-fold risk (OR = 0.46, 95% CI: 0.357-0.59, P < 0.01) and 0.7-fold risk (OR = 0.707, 95% CI: 0.534-0.937, P = 0.015) of the occurrence of SZ,. When subjects were divided by gender, rs1799971 remained significant difference only in males (OR = 0.309, 95% CI: 0.218-0.439 for G allele, P < 0.01), and rs2075572 only in females (OR = 0.399, 95% CI: 0.246-0.648 for G allele, P < 0.01). In secondary analysis with subsets of patients, the G allele of rs1799971 (compared to the A allele) was associated with a decreased risk of all patients and male patients with apathy symptoms (OR = 0.086, 95% CI: 0.048-0.151, P = 0.01; OR = 0.083, 95% CI: 0.045-0.153, P < 0.01), and the G allele of rs2075572 (compared to the C allele) was associated with a decreased risk of all patients and female patients with positive family history (OR = 0.468, 95% CI: 0.309-0.71, P < 0.01; OR = 0.34, 95% CI: 0.195-0.593, P < 0.01). In addition, haplotype analysis revealed that two SNP haplotypes (A-C-C-G and G-C-C-A) were associated with decreased risks of SZ (P < 0.01). The other two (G-C-C-G and G-G-C-G) with increased risks of SZ (P < 0.01).

Conclusions

The present study demonstrated for the first time that the OPRM1 polymorphism may be a risk factor for schizophrenia in the Han Chinese. Further studies are needed to give a global view of this polymorphism in pathogenesis of schizophrenia in a large-scale sample, family-based association design or well-defined subgroups of schizophrenia.
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Literature
1.
Ross CA, Margolis RL, Reading SA, Pletnikov M, Coyle JT: Neurobiology of schizophrenia. Neuron. 2006, 52 (1): 139-153. 10.1016/j.neuron.2006.09.015.PubMed
2.
Owen MJ, Craddock N, O'Donovan MC: Schizophrenia: genes at last?. Trends Genet. 2005, 21 (9): 518-525. 10.1016/j.tig.2005.06.011.PubMed
3.
Caldwell CB, Gottesman I: Schizophrenics kill themselves too: a review of risk factors for suicide. Schizophr Bull. 1990, 16 (4): 571-589. 10.1093/schbul/16.4.571.PubMed
4.
Doi N, Hoshi Y, Itokawa M, Usui C, Yoshikawa T, Tachikawa H: Persistence criteria for susceptibility genes for schizophrenia: a discussion from an evolutionaryviewpoint. PLoS One. 2009, 4 (11): e7799-10.1371/journal.pone.0007799.PubMedPubMedCentral
5.
Sanders AR, Duan J, Levinson DF, Shi J, He D, Hou C: No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics. Am J Psychiatry. 2008, 165 (4): 497-506. 10.1176/appi.ajp.2007.07101573.PubMed
6.
Need AC, Ge D, Weale ME, Maia J, Feng S, Heinzen EL, Shianna KV, Yoon W, Kasperaviciūte D, Gennarelli M: A genome-wide investigation of SNPs and CNVs in schizophrenia. PLoS Genet. 2009, 5 (2): e1000373-10.1371/journal.pgen.1000373.PubMedPubMedCentral
7.
O'Donovan MC, Craddock N, Norton N, Williams H, Peirce T, Moskvina V, Nikolov I, Hamshere M, Carroll L, Georgieva L: Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat Genet. 2008, 40 (9): 1053-1055. 10.1038/ng.201.PubMed
8.
Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB: Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science. 2008, 320 (5875): 539-543. 10.1126/science.1155174.PubMed
9.
Williams HJ, Owen MJ, O'Donovan MC: New findings from genetic association studies of schizophrenia. J Hum Genet. 2009, 54 (1): 9-14. 10.1038/jhg.2008.7.PubMed
10.
Delfs JM, Kong H, Mestek A, Chen Y, Yu L, Reisine T, Chesselet MF: Expression of mu opioid receptor mRNA in rat brain: an in situ hybridization study at the single celllevel. J Comp Neurol. 1994, 345 (1): 46-68. 10.1002/cne.903450104.PubMed
11.
Uhl GR, Sora I, Wang Z: The mu opiate receptor as a candidate gene for pain: polymorphisms, variations in expression, nociception, and opiate responses. Proc Natl Acad Sci USA. 1999, 96 (14): 7752-7755. 10.1073/pnas.96.14.7752.PubMedPubMedCentral
12.
Matthes HW, Maldonado R, Simonin F, Valverde O, Slowe S, Kitchen I, Befort K, Dierich A, Le Meur M, Dollé P, Tzavara E: Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking themu-opioid-receptor gene. Nature. 1996, 383 (6603): 819-823. 10.1038/383819a0.PubMed
13.
Sora I, Takahashi N, Funada M, Ujike H, Revay RS, Donovan DM, Miner LL, Uhl GR: Opiate receptor knockout mice define mu receptor roles in endogenous nociceptive responses and morphine-induced analgesia. Proc Natl Acad Sci. 1997, 94 (4): 1544-1549. 10.1073/pnas.94.4.1544.PubMedPubMedCentral
14.
Ide S, Kobayashi H, Ujike H, Ozaki N, Sekine Y, Inada T, Harano M, Komiyama T, Yamada M, Iyo M: Linkage disequilibrium and association with methamphetamine dependence/psychosis of mu-opioid receptor gene polymorphisms. Pharmacogenomics J. 2006, 6 (3): 179-188. 10.1038/sj.tpj.6500355.PubMed
15.
Ide S, Kobayashi H, Tanaka K, Ujike H, Sekine Y, Ozaki N, Inada T, Harano M, Komiyama T, Yamada M: Gene polymorphisms of the mu opioid receptor in methamphetamine abusers. Ann N Y Acad Sci. 2004, 1025: 316-324. 10.1196/annals.1316.039.PubMed
16.
Ikeda K, Ide S, Han W, Hayashida M, GR U, Sora I: How individual sensitivity to opiates can be predicted by gene analyses. Trends Pharmacol Sci. 2005, 26 (6): 311-317. 10.1016/j.tips.2005.04.001.PubMed
17.
Bond C, LaForge KS, Tian M, Melia D, Zhang S, Borg L, Gong J, Schluger J, Strong JA, Leal SM: Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci USA. 1998, 95 (16): 9608-9613. 10.1073/pnas.95.16.9608.PubMedPubMedCentral
18.
Ohmori O, Shinkai T, Hori H, Kojima H, Nakamura J: Polymorphisms of mu and delta opioid receptor genes and tardive dyskinesia in patients with schizophrenia. Schizophr Res. 2001, 52 (1–2): 137-138.PubMed
19.
Tan EC, Chong SA, Mahendran R, Tan CH, Teo YY: Mu opioid receptor gene polymorphism and neuroleptic-induced tardive dyskinesia in patients with schizophrenia. Schizophr Res. 2003, 65 (1): 61-63. 10.1016/S0920-9964(02)00491-7.PubMed
20.
Kroslak T, Laforge KS, Gianotti RJ, Ho A, Nielsen DA, Kreek MJ: The single nucleotide polymorphism A118G alters functional properties of the human mu opioid receptor. J Neurochem. 2007, 103 (1): 77-87.PubMed
21.
Bare L, Mansson E, Yang D: Expression of two variants of the human mu opioid receptor mRNA in SK-N-SH cells and human brain. FEBS Lett. 1994, 354 (2): 213-216. 10.1016/0014-5793(94)01129-X.PubMed
22.
Pan L, Xu J, Yu R, Xu M, Pan Y, Pasternak G: Identification and characterization of six new alternatively spliced variants of the human mu opioid receptor gene. Oprm Neurosci. 2005, 133 (1): 209-220. 10.1016/j.neuroscience.2004.12.033.
23.
Pan Y: Identification of alternatively spliced variants from opioid receptor genes. Meth Mol Med. 2003, 84: 65-75.
24.
Curley AA, Arion D, Volk DW, Asafu-Adjei JK, Sampson AR, Fish KN, Lewis DA: Cortical deficits of glutamic acid decarboxylase 67 expression in schizophrenia: clinical, protein, and cell type-specific features. Am J Psychiatry. 2011, 168 (9): 921-929. 10.1176/appi.ajp.2011.11010052.PubMedPubMedCentral
25.
Fung SJ, Webster MJ, Sivagnanasundaram S, Duncan C, Elashoff M, Weickert CS: Expression of interneuron markers in the dorsolateral prefrontal cortex of the developing humanand in schizophrenia. Am J Psychiatry. 2010, 167 (12): 1479-1488. 10.1176/appi.ajp.2010.09060784.PubMed
26.
Hashimoto T, Volk DW, Eggan SM, Mirnics K, Pierri JN, Sun Z, Sampson AR, Lewis DA: Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia. J Neurosci. 2003, 23 (15): 6315-6326.PubMed
27.
Mellios N, Huang HS, Baker SP, Galdzicka M, Ginns E, Akbarian S: Molecular determinants of dysregulated GABAergic gene expression in the prefrontal cortex ofsubjects with schizophrenia. Biol Psychiatry. 2009, 65 (12): 1006-1014. 10.1016/j.biopsych.2008.11.019.PubMed
28.
Morris HM, Hashimoto T, Lewis DA: Alterations in somatostatin mRNA expression in the dorsolateral prefrontal cortex of subjects withschizophrenia or schizoaffective disorder. Cereb Cortex. 2008, 18 (7): 1575-1587.PubMedPubMedCentral
29.
Reichenberg A, Caspi A, Harrington H, Houts R, Keefe RS, Murray RM, Poulton R, Moffitt TE: Static and dynamic cognitive deficits in childhood preceding adult schizophrenia: a 30-year study. Am J Psychiatry. 2010, 167 (2): 160-169. 10.1176/appi.ajp.2009.09040574.PubMedPubMedCentral
30.
Tanaka S, Matsunaga H, Kimura M, Tatsumi K, Hidaka Y, Takano T, Uema T, Takeda M, Amino N: Autoantibodies against four kinds of neurotransmitter receptors in psychiatric disorders. J Neuroimmunol. 2003, 141 (1–2): 155-164.PubMed
31.
Trezza V, Damsteegt R, Achterberg EJ, Vanderschuren LJ: Nucleus accumbens μ-opioid receptors mediate social reward. J Neurosci. 2011, 31 (17): 6362-6370. 10.1523/JNEUROSCI.5492-10.2011.PubMedPubMedCentral
32.
Volk DW, Radchenkova PV, Walker EM, Sengupta EJ, Lewis DA: Cortical Opioid Markers in Schizophrenia and across Postnatal Development. Cereb Cortex. 2012, 22 (5): 1215-1223. 10.1093/cercor/bhr202.PubMed
33.
Tan EC, Chong SA, Mahendran R, Tan CH, Teo YY: Mu opioid receptor gene polymorphism and neuroleptic-induced tardive dyskinesia in patientswith schizophrenia. Schizophr Res. 2003, 65 (1): 61-63. 10.1016/S0920-9964(02)00491-7.PubMed
34.
Zhang Y, Wang D, Johnson AD, Papp AC, Sadée W: Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G. J Biol Chem. 2005, 280 (38): 32618-32624. 10.1074/jbc.M504942200.PubMed
35.
Goswami S, Mattoo SK, Basu D, Singh G: Substance-abusing schizophrenics: do they self-medicate?. Am J Addict. 2004, 13 (2): 139-150. 10.1080/10550490490435795.PubMed
36.
Amorim P, Lecrubier Y, Weiller E, Hergueta T, Sheehan D: DSM-IH-R Psychotic Disorders: procedural validity of the Mini International Neuropsychiatric Interview (MINI). Concordance and causes for discordance with the CIDI. Eur Psychiatr. 1998, 13 (1): 26-34. 10.1016/S0924-9338(97)86748-X.
37.
Alves TM, Pereira JC, Elkis H: The psychopathological factors of refractory schizophrenia. Rev Bras Psiquiatr. 2005, 27 (2): 108-112. 10.1590/S1516-44462005000200007.PubMed
38.
Overall JE: Rating session. Video taped interviews and BPRS ratings. Psychopharmacol Bull. 1975, 11 (1): 15-PubMed
39.
Corrêa H, Duval F, Mokrani MC, Bailey P, Trémeau F, Staner L, Diep TS, Crocq MA, Macher JP: Serotonergic function and suicidal behavior in schizophrenia. Schizophr Res. 2002, 56: 75-85. 10.1016/S0920-9964(01)00181-5. 1-2PubMed
40.
Zhang C, Fang Y, Xie B, Cheng W, Du Y, Wang D, Yu S: DNA methyltransferase 3B gene increases risk of early onset schizophrenia. Neurosci Lett. 2009, 462 (3): 308-311. 10.1016/j.neulet.2009.06.085.PubMed
41.
Zhang C, Fang Y, Xie B, Cheng W, Du Y, Wang D, Yu S: No genetic association between dopamine D1 receptor gene and [early onset] schizophrenia. Psychiatr Res. 2010, 177 (3): 350-353. 10.1016/j.psychres.2009.12.011.
42.
Kumra S, Charles Schulz S: Editorial: research progress in early-onset schizophrenia. Schizophr Bull. 2008, 34 (1): 15-17.PubMed
43.
Devylder JE, Lukens EP: Family history of schizophrenia as a risk factor for axis I psychiatric conditions. J Psychiatr Res. 2013, 47 (2): 181-187. 10.1016/j.jpsychires.2012.09.023.PubMed
44.
Purcell S, Cherny S, Sham P: Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics. 2003, 19 (1): 149-150. 10.1093/bioinformatics/19.1.149.PubMed
45.
Shi YY, He L: SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res. 2005, 15 (2): 97-98. 10.1038/sj.cr.7290272.PubMed
46.
Li J, Ji L: Adjusting multiple testing in multilocus analyses using the eigenvalues of a correlation matrix.Heredity (Edinb). Heredity (Edinb). 2005, 95 (3): 221-227. 10.1038/sj.hdy.6800717.
47.
Nyholt DR: A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet. 2004, 74 (4): 765-769. 10.1086/383251.PubMedPubMedCentral
48.
Zhang H, Luo X, Kranzler HR, Lappalainen J, Yang BZ, Krupitsky E, Zvartau E, Gelernter J: Association between two mu-opioid receptor gene (OPRM1) haplotype blocks and drug or alcohol dependence. Hum Mol Genet. 2006, 15 (6): 807-819. 10.1093/hmg/ddl024.PubMedPubMedCentral
49.
Káradóttir R, Attwell D: Neurotransmitter receptors in the life and death of oligodendrocytes. Neuroscience. 2007, 145 (4): 1426-1438. 10.1016/j.neuroscience.2006.08.070.PubMedPubMedCentral
50.
Káradóttir R, Cavelier P, Bergersen LH, Attwell D: NMDA receptors are expressed in oligodendrocytes and activated in ischaemia. Nature. 2005, 438 (7071): 1162-1166. 10.1038/nature04302.PubMedPubMedCentral
51.
Serý O, Prikryl R, Castulík L, St'astný F: A118G polymorphism of OPRM1 gene is associated with schizophrenia. J Mol Neurosci. 2010, 41 (1): 219-222. 10.1007/s12031-010-9327-z.PubMed
52.
Leung A, Chue P: Sex differences in schizophrenia, a review of the literature. Acta Psychiatr Scand Suppl. 2000, 401: 3-38.PubMed
53.
Hoenicka J, Garrido E, Martínez I, Ponce G, Aragüés M, Rodríguez-Jiménez R, España-Serrano L, Alvira-Botero X, Santos JL, Rubio G: Gender-specific COMT Val158Met polymorphism association in Spanish schizophrenic patients. Am J Med Genet B Neuropsychiatr Genet. 2010, 153B (1): 79-85.PubMed
54.
Wang LH, Chen JY, Liou YJ, Wang YC, Lai IC, Liao DL, Chen CH: Association of missense variants of the PRKC, apoptosis, WT1, regulator (PAWR) gene with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2008, 32 (3): 870-875. 10.1016/j.pnpbp.2008.01.003.PubMed
Metadata
Title
Association study of OPRM1 polymorphisms with Schizophrenia in Han Chinese population
Authors
Saidan Ding
Bicheng Chen
Yong Zheng
Qin Lu
Leping Liu
Qǐ-Chuan Zhuge
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2013
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/1471-244X-13-107

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