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Lack of association between dopamine D3 receptor Ser9Gly polymorphism and schizophrenia in Han Chinese population

Published online by Cambridge University Press:  24 June 2014

Hsin-An Chang ,
Ru-Band Lu ,
Wei-Wen Lin ,
Chuan-Chia Chang ,
Chih-Lun Chen ,
Mee-Jen Shy  and
San-Yuan Huang
Hsin-An Chang
Affiliation:
Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan
Ru-Band Lu
Affiliation:
Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China
Wei-Wen Lin
Affiliation:
Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan
Chuan-Chia Chang
Affiliation:
Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan
Chih-Lun Chen
Affiliation:
Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan
Mee-Jen Shy
Affiliation:
Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan
San-Yuan Huang*
Affiliation:
Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan
*
Dr San-Yuan Huang, Department of Psychiatry, Tri-Service General Hospital, No. 325, Cheng-Kung Road, Sec. 2, Nei-Hu District, Taipei 114, Taiwan, Republic of China. Tel: +886-2-8792-7220; Fax: +886-2-8792-6715; E-mail: [email protected]
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Abstract

Background:

The Ser9Gly polymorphism in dopamine D3 receptor gene (DRD3) was considered an important factor in the pathogenesis of schizophrenia. Allele and genotype frequencies of this polymorphism were studied in different ethnic groups of schizophrenic patients. However, the results have been inconclusive.

Objective:

To determine whether the DRD3 Ser9Gly polymorphism is associated with schizophrenia or influences its psychopathological symptoms in Han Chinese population.

Method:

We recruited 256 schizophrenic patients and 285 normal controls matched for gender, age and ethnicity. Pretreatment psychotic symptoms were evaluated with the Positive and Negative Symptom Scale (PANSS) in 128 acutely exacerbated schizophrenic in-patients. Genotyping of Ser9Gly polymorphism was performed with a polymerase chain reaction restriction fragment length polymorphism method and reconfirmed by a direct sequencing technique.

Results:

No significant difference was found between either patients with schizophrenia or with more homogeneous schizophrenic subgroups and healthy controls in genotype distributions and allele frequencies for the DRD3 Ser9Gly polymorphism. Similarly, DRD3 Ser9Gly genotype differences failed to reach significance in PANSS global, positive, negative and general symptoms scores. There is a trend (P = 0.064) towards higher PANSS positive symptoms scores in subjects carrying the Gly/Gly genotype.

Conclusion:

This study does not support the role of DRD3 Ser9Gly polymorphism in increasing genetic risk for schizophrenia in Han Chinese population. Still, there is a possibility that the DRD3 Ser9Gly variant may reflect genetic variation of severity of positive symptoms in acutely exacerbated schizophrenia. Further studies are warranted to investigate the effect of the DRD3 Ser9Gly polymorphism in relation to longer time course of schizophrenia, including treatment response to antipsychotics.

Keywords

associationdopamine D3 receptor genepolymorphismschizophrenia
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 19 , Issue 6 , December 2007 , pp. 344 - 350
Copyright
Copyright © 2007 Blackwell Munksgaard

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References

Davis, KL, Kahn, RS, Ko, G, Davidson, M. Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry 1991;148:1474–1486. Google ScholarPubMed
van Rossum, JM. The significance of dopamine-receptor blockade for the mechanism of action of neuroleptic drugs. Arch Int Pharmacodyn Ther 1966;160:492–494. Google ScholarPubMed
Sokoloff, P, Giros, B, Martres, MP, Bouthenet, ML, Schwartz, JC. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 1990;347:146–151. CrossRefGoogle ScholarPubMed
Gurevich, EV, Bordelon, Y, Shapiro, RM, Arnold, SE, Gur, RE, Joyce, JN. Mesolimbic dopamine D3 receptors and use of antipsychotics in patients with schizophrenia. A postmortem study. Arch Gen Psychiatry 1997;54:225–232. CrossRefGoogle ScholarPubMed
Schmauss, C, Haroutunian, V, Davis, KL, Davidson, M. Selective loss of dopamine D3-type receptor mRNA expression in parietal and motor cortices of patients with chronic schizophrenia. Proc Natl Acad Sci U S A 1993;90:8942–8946. CrossRefGoogle ScholarPubMed
Lannfelt, L, Sokoloff, P, Martres, MPet al. Amino acid substitution in the dopamine D3 receptor as a useful polymorphism for investigating psychiatric disorders. Psychiatr Genet 1992;2:249–256. CrossRefGoogle Scholar
Lundstrom, K, Turpin, MP. Proposed schizophrenia-related gene polymorphism: expression of the Ser9Gly mutant human dopamine D3 receptor with the Semliki Forest virus system. Biochem Biophys Res Commun 1996;225:1068–1072. CrossRefGoogle ScholarPubMed
Coon, H, Byerley, W, Holik, Jet al. Linkage analysis of schizophrenia with five dopamine receptor genes in nine pedigrees. Am J Hum Genet 1993;52:327–334. Google ScholarPubMed
Wiese, C, Lannfelt, L, Kristbjarnarson, Het al. No evidence of linkage between schizophrenia and D3 dopamine receptor gene locus in Icelandic pedigrees. Psychiatry Res 1993;46:69–78. CrossRefGoogle ScholarPubMed
Ishiguro, H, Okuyama, Y, Toru, M, Arinami, T. Mutation and association analysis of the 5’ region of the dopamine D3 receptor gene in schizophrenia patients: identification of the Ala38Thr polymorphism and suggested association between DRD3 haplotypes and schizophrenia. Mol Psychiatry 2000;5:433–438. CrossRefGoogle ScholarPubMed
Shaikh, S, Collier, DA, Sham, PCet al. Allelic association between a Ser-9-Gly polymorphism in the dopamine D3 receptor gene and schizophrenia. Hum Genet 1996;97:714–719. CrossRefGoogle ScholarPubMed
Nimgaonkar, VL, Sanders, AR, Ganguli, Ret al. Association study of schizophrenia and the dopamine D3 receptor gene locus in two independent samples. Am J Med Genet 1996;67:505–514. 3.0.CO;2-G>CrossRefGoogle ScholarPubMed
Spurlock, G, Williams, J, Mcguffin, Pet al. European Multicentre Association Study of Schizophrenia: a study of the DRD2 Ser311Cys and DRD3 Ser9Gly polymorphisms. Am J Med Genet 1998;81:24–28. 3.0.CO;2-N>CrossRefGoogle ScholarPubMed
Meszaros, K, Lenzinger, E, Hornik, Ket al. Association study of schizophrenia spectrum disorders and dopamine D3 receptor gene: is schizoaffective disorder special? Psychiatry Res 2000;96:179–183. CrossRefGoogle Scholar
Williams, J, Spurlock, G, Holmans, Pet al. A meta-analysis and transmission disequilibrium study of association between the dopamine D3 receptor gene and schizophrenia. Mol Psychiatry 1998;3:141–149. CrossRefGoogle ScholarPubMed
Ebstein, RP, Macciardi, F, Heresco-Levi, Uet al. Evidence for an association between the dopamine D3 receptor gene DRD3 and schizophrenia. Hum Hered 1997;47:6–16. CrossRefGoogle ScholarPubMed
Anney, RJ, Rees, MI, Bryan, Eet al. Characterisation, mutation detection, and association analysis of alternative promoters and 5’ UTRs of the human dopamine D3 receptor gene in schizophrenia. Mol Psychiatry 2002;7:493–502. CrossRefGoogle ScholarPubMed
Jonsson, EG, Kaiser, R, Brockmoller, J, Nimgaonkar, VL, Crocq, MA. Meta-analysis of the dopamine D3 receptor gene (DRD3) Ser9Gly variant and schizophrenia. Psychiatr Genet 2004;14:9–12. CrossRefGoogle ScholarPubMed
Ventriglia, M, Bocchio Chiavetto, L, Bonvicini, Cet al. Allelic variation in the human prodynorphin gene promoter and schizophrenia. Neuropsychobiology 2002;46:17–21. CrossRefGoogle ScholarPubMed
Wong, AH, Buckle, CE, Van Tol, HH. Polymorphisms in dopamine receptors: what do they tell us? Eur J Pharmacol 2000;410:183–203. CrossRefGoogle ScholarPubMed
Jonsson, EG, Flyckt, L, Burgert, Eet al. Dopamine D3 receptor gene Ser9Gly variant and schizophrenia: association study and meta-analysis. Psychiatr Genet 2003;13:1–12. CrossRefGoogle ScholarPubMed
Yang, L, Li, T, Wiese, Cet al. No association between schizophrenia and homozygosity at the D3 dopamine receptor gene. Am J Med Genet 1993;48:83–86. CrossRefGoogle ScholarPubMed
Saha, N, Tsoi, WF, Low, PS, Basair, J, Tay, JS. Lack of association of the dopamine D3 receptor gene polymorphism (BalI) in Chinese schizophrenic males. Psychiatr Genet 1994;4:201–204. CrossRefGoogle ScholarPubMed
Chen, CH, Liu, MY, Wei, FC, Koong, FJ, Hwu, HG, Hsiao, KJ. Further evidence of no association between Ser9Gly polymorphism of dopamine D3 receptor gene and schizophrenia. Am J Med Genet 1997;74:40–43. 3.0.CO;2-Z>CrossRefGoogle ScholarPubMed
Mant, R, Williams, J, Asherson, P, Parfitt, E, Mcguffin, P, Owen, MJ. Relationship between homozygosity at the dopamine D3 receptor gene and schizophrenia. Am J Med Genet 1994;54:21–26. CrossRefGoogle ScholarPubMed
Steen, VM, Lovlie, R, Macewan, T, Mccreadie, RG. Dopamine D3-receptor gene variant and susceptibility to tardive dyskinesia in schizophrenic patients. Mol Psychiatry 1997;2:139–145. CrossRefGoogle ScholarPubMed
Segman, R, Neeman, T, Heresco-Levy, Uet al. Genotypic association between the dopamine D3 receptor and tardive dyskinesia in chronic schizophrenia. Mol Psychiatry 1999;4:247–253. CrossRefGoogle ScholarPubMed
Eichhammer, P, Albus, M, Borrmann-Hassenbach, Met al. Association of dopamine D3-receptor gene variants with neuroleptic induced akathisia in schizophrenic patients: a generalization of Steen’s study on DRD3 and tardive dyskinesia. Am J Med Genet 2000;96:187–191. 3.0.CO;2-8>CrossRefGoogle Scholar
Dahmen, N, Muller, MJ, Germeyer, Set al. Genetic polymorphisms of the dopamine D2 and D3 receptor and neuroleptic drug effects in schizophrenic patients. Schizophr Res 2001;49:223–225. CrossRefGoogle ScholarPubMed
Cloninger, CR, Adolfsson, R, Svrakic, NM. Mapping genes for human personality. Nat Genet 1996;12:3–4. CrossRefGoogle ScholarPubMed
Risch, N. Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet 1990;46:222–228. Google ScholarPubMed
Inada, T, Sugita, T, Dobashi, Iet al. Dopamine D3 receptor gene polymorphism and the psychiatric symptoms seen in first-break schizophrenic patients. Psychiatr Genet 1995;5:113–116. CrossRefGoogle ScholarPubMed
Serretti, A, Lattuada, E, Cusin, C, Lilli, R, Lorenzi, C, Smeraldi, E. Dopamine D3 receptor gene not associated with symptomatology of major psychoses. Am J Med Genet 1999;88:476–480. 3.0.CO;2-9>CrossRefGoogle Scholar
Szekeres, G, Keri, S, Juhasz, Aet al. Role of dopamine D3 receptor (DRD3) and dopamine transporter (DAT) polymorphism in cognitive dysfunctions and therapeutic response to atypical antipsychotics in patients with schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2004;124:1–5. CrossRefGoogle Scholar
Reynolds, GP, Yao, Z, Zhang, X, Sun, J, Zhang, Z. Pharmacogenetics of treatment in first-episode schizophrenia: D3 and 5-HT2C receptor polymorphisms separately associate with positive and negative symptom response. Eur Neuropsychopharmacol 2005;15:143–151. CrossRefGoogle ScholarPubMed
Merikangas, KR, Stevens, DE, Fenton, Bet al. Co-morbidity and familial aggregation of alcoholism and anxiety disorders. Psychol Med 1998;28:773–788. CrossRefGoogle ScholarPubMed
Endicott, J, Spitzer, RL. A diagnostic interview: the schedule for affective disorders and schizophrenia. Arch Gen Psychiatry 1978;35:837–844. CrossRefGoogle ScholarPubMed
American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edn. Washington DC: American Psychiatric Press, 1994. Google Scholar
Huang, SY, Lin, WW, Ko, HCet al. Possible interaction of alcohol dehydrogenase and aldehyde dehydrogenase genes with the dopamine D2 receptor gene in anxiety-depressive alcohol dependence. Alcohol Clin Exp Res 2004;28:374–384. CrossRefGoogle ScholarPubMed
Kay, SR, Fiszbein, A, Opler, LA. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–276. CrossRefGoogle ScholarPubMed
Wang, ZW, Fang, YR, Hong, W, Wang, DX, Jing, SD. Association study of NOTCH4 gene polymorphisms with schizophrenia and mood disorders in mixed pedigrees. Yi Chuan 2005;27:865–868. Google ScholarPubMed
Malhotra, AK, Goldman, D, Buchanan, RWet al. The dopamine D3 receptor (DRD3) Ser9Gly polymorphism and schizophrenia: a haplotype relative risk study and association with clozapine response. Mol Psychiatry 1998;3:72–75. CrossRefGoogle ScholarPubMed
Buchner, A, Faul, F, Erdfelder, E. G-power: a priori, post hoc, and compromise power analyses for the Macintosh, version 2.1.1. Trier: Germany University of Trier, 1996. Google Scholar
Hawi, Z, Mccabe, U, Straub, REet al. Examination of new and reported data of the DRD3/MscI polymorphism: no support for the proposed association with schizophrenia. Mol Psychiatry 1998;3:150–155. CrossRefGoogle ScholarPubMed
Nurnberger, JI Jr. Implications of multifactorial inheritance for identification of genetic mechanisms in major psychiatric disorders. Psychiatr Genet 2002;12:121–126. CrossRefGoogle ScholarPubMed
Talkowski, ME, Mansour, H, Chowdari, KVet al. Novel, replicated associations between dopamine D3 receptor gene polymorphisms and schizophrenia in two independent samples. Biol Psychiatry 2006;60:570–577. CrossRefGoogle ScholarPubMed