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Meta-analysis of the HTR2A–1354C/T polymorphism in schizophrenia and bipolar disorder

Published online by Cambridge University Press:  23 May 2013

Lian Gu ,
Jinjing Tan ,
Li Su ,
Yuwang Qin ,
Jianxiong Long ,
Qing Chen ,
Juanjuan Xie ,
Baoyun liang ,
Yan Yan  and
Guangliang Wu
Lian Gu*
Affiliation:
Department of Internal Neurology, First Affiliated Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
Jinjing Tan
Affiliation:
Department of Internal Neurology, First Affiliated Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
Li Su
Affiliation:
School of Public Health of Guangxi Medical University, Nanning, Guangxi, China
Yuwang Qin*
Affiliation:
Guangxi University of Chinese Medicine, Nanning, Guangxi, China
Jianxiong Long
Affiliation:
School of Public Health of Guangxi Medical University, Nanning, Guangxi, China
Qing Chen
Affiliation:
Department of Internal Neurology, First Affiliated Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
Juanjuan Xie
Affiliation:
Department of Internal Neurology, First Affiliated Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
Baoyun liang
Affiliation:
Department of Internal Neurology, First Affiliated Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
Yan Yan
Affiliation:
Department of Internal Neurology, First Affiliated Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
Guangliang Wu
Affiliation:
Department of Internal Neurology, First Affiliated Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
*
Lian Gu, Department of Internal Neurology, First Affiliated Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi, China. E-mail: gulian2012@163.com
Yuwang Qin, Guangxi University of Chinese Medicine, 179 Mingxiu East Road, Nanning, Guangxi, China. E-mail: qinyuwang2012@yahoo.cn
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Abstract

Objective

Schizophrenia (SCZ) and bipolar disorder (BD) are common psychotic disorders, which show some overlaps in genetic aetiology. Researchers have conducted a number of studies to investigate the relationship between SCZ and the 1354C/T genetic polymorphism of 5-hydroxytryptamine receptor 2A (HTR2A–1354C/T), as well as the associations between BD and the HTR2A–1354C/T polymorphism. However, the results were conflicting. To provide a more robust estimate about the effects of the HTR2A–1354C/T polymorphism on the risk of these two psychotic disorders, we performed this meta-analysis.

Methods

We used the pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) to investigate the relationships between SCZ and the 1354C/T polymorphism of HTR2A, as well as the associations between BD and HTR2A–1354C/T. Publication bias was tested by Begg's test and inverted funnel plot, and heterogeneity was checked by Cochran's Q statistic and the inconsistency index (I2).

Results

Eight studies were concerned with SCZ, analysing a cumulative total of 2953 cases and 3153 controls; six papers studied BD, using a total of 923 cases and 928 controls. There was no significant association found between HTR2A–1354C/T and SCZ in the overall population (T allele vs. C allele, OR = 1.035, 95% CI 0.912–1.175, p = 0.596) or in the subgroups Caucasian population and Asian population. Moreover, there was no significant association between the HTR2A–1354C/T polymorphism and BD in the overall population (T allele vs. C allele, OR = 1.038, 95% CI = 0.607–1.772, p = 0.892).

Conclusion

On the basis of these results, the HTR2A–1354C/T polymorphism is unlikely to be a risk factor for SCZ and BD.

Keywords

bipolar disorderHTR2A–1354C/Tmeta-analysisschizophrenia
Type
Review article
Information
Acta Neuropsychiatrica , Volume 25 , Issue 6 , December 2013 , pp. 311 - 319
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013 

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Footnotes

Lian Gu, Jinjing Tan and Li Su are co-first authors for this article.

Lian Gu and Yuwang Qin are co-corresponding authors for this article.

References

1.Van Os, J, Kapur, S. Schizophrenia. Lancet 2009;374:635–645.CrossRefGoogle ScholarPubMed
2.Ketter, TA. Diagnostic features, prevalence, and impact of bipolar disorder. J Clin Psychiatry 2010;71:e14.CrossRefGoogle ScholarPubMed
3.Kravariti, E, Dixon, T, Frith, C, Murray, R, McGuire, P. Association of symptoms and executive function in schizophrenia and bipolar disorder. Schizophr Res 2005;74:221–231.CrossRefGoogle ScholarPubMed
4.Martinez-Aran, A, Vieta, E, Colom, Fet al. Neuropsychological performance in depressed and euthymic bipolar patients. Neuropsychobiology 2002;46(Suppl. 1):16–21.CrossRefGoogle ScholarPubMed
5.Seidman, LJ, Kremen, WS, Koren, D, Faraone, SV, Goldstein, JM, Tsuang, MT. A comparative profile analysis of neuropsychological functioning in patients with schizophrenia and bipolar psychoses. Schizophr Res 2002;53:31–44.CrossRefGoogle ScholarPubMed
6.Van Os, J, Gilvarry, C, Bale, Ret al. A comparison of the utility of dimensional and categorical representations of psychosis. UK700 Group. Psychol Med 1999;29:595–606.CrossRefGoogle ScholarPubMed
7.Cardno, AG, Rijsdijk, FV, Sham, PC, Murray, RM, McGuffin, P. A twin study of genetic relationships between psychotic symptoms. Am J Psychiatry 2002;159:539–545.CrossRefGoogle ScholarPubMed
8.Craddock, N, O'Donovan, MC, Owen, MJ. The genetics of schizophrenia and bipolar disorder: dissecting psychosis. J Med Genet 2005;42:193–204.CrossRefGoogle ScholarPubMed
9.Shih, RA, Belmonte, PL, Zandi, PP. A review of the evidence from family, twin and adoption studies for a genetic contribution to adult psychiatric disorders. Int Rev Psychiatry 2004;16:260–283.CrossRefGoogle ScholarPubMed
10.Gershon, ES, DeLisi, LE, Hamovit, Jet al. A controlled family study of chronic psychoses. Schizophrenia and schizoaffective disorder. Arch Gen Psychiatry 1988;45:328–336.CrossRefGoogle ScholarPubMed
11.Farmer, AE, McGuffin, P, Gottesman, II. Twin concordance for DSM-III schizophrenia. Scrutinizing the validity of the definition. Arch Gen Psychiatry 1987;44:634–641.CrossRefGoogle ScholarPubMed
12.Kendler, KS, Masterson, CC, Davis, KL. Psychiatric illness in first-degree relatives of patients with paranoid psychosis, schizophrenia and medical illness. Br J Psychiatry 1985;147:524–531.CrossRefGoogle ScholarPubMed
13.Kendler, KS. Twin studies of psychiatric illness. Current status and future directions. Arch Gen Psychiatry 1993;50:905–915.CrossRefGoogle ScholarPubMed
14.Maier, W, Lichtermann, D, Minges, Jet al. Continuity and discontinuity of affective disorders and schizophrenia. Results of a controlled family study. Arch Gen Psychiatry 1993;50:871–883.CrossRefGoogle ScholarPubMed
15.Craddock, N, O'Donovan, MC, Owen, MJ. Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology. Schizophr Bull 2006;32:9–16.CrossRefGoogle ScholarPubMed
16.Potash, JB. Carving chaos: genetics and the classification of mood and psychotic syndromes. Harv Rev Psychiatry 2006;14:47–63.CrossRefGoogle ScholarPubMed
17.Olgiati, P, Mandelli, L, Lorenzi, Cet al. Schizophrenia: genetics, prevention and rehabilitation. Acta Neuropsychiatrica 2009;21:109–120.CrossRefGoogle ScholarPubMed
18.Williams, HJ, Craddock, N, Russo, Get al. Most genome-wide significant susceptibility loci for schizophrenia and bipolar disorder reported to date cross-traditional diagnostic boundaries. Hum Mol Genet 2011;20:387–391.CrossRefGoogle ScholarPubMed
19.Veenstra-VanderWeele, J, Anderson, GM, Cook, EH JrPharmacogenetics and the serotonin system: initial studies and future directions. Eur J Pharmacol 2000;410:165–181.CrossRefGoogle ScholarPubMed
20.Inayama, Y, Yoneda, H, Sakai, Tet al. Positive association between a DNA sequence variant in the serotonin 2A receptor gene and schizophrenia. Am J Med Genet 1996;67:103–105.3.0.CO;2-S>CrossRefGoogle ScholarPubMed
21.Hansenne, M, Pitchot, W, Ansseau, M. Serotonin, personality and borderline personality disorder. Acta Neuropsychiatrica 2002;14:66–70.CrossRefGoogle ScholarPubMed
22.Meltzer, HY, Li, Z, Kaneda, Y, Ichikawa, J. Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:1159–1172.CrossRefGoogle ScholarPubMed
23.Geyer, MA, Vollenweider, FX. Serotonin research: contributions to understanding psychoses. Trends Pharmacol Sci 2008;29:445–453.CrossRefGoogle ScholarPubMed
24.Hoyer, D, Clarke, DE, Fozard, JRet al. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol Rev 1994;46:157–203.Google ScholarPubMed
25.Yates, M, Leake, A, Candy, JM, Fairbairn, AF, McKeith, IG, Ferrier, IN. 5HT2 receptor changes in major depression. Biol Psychiatry 1990;27:489–496.CrossRefGoogle ScholarPubMed
26.Meltzer, HY, Massey, BW, Horiguchi, M. Serotonin receptors as targets for drugs useful to treat psychosis and cognitive impairment in schizophrenia. Curr Pharm Biotechnol 2012;13:1572–1586.CrossRefGoogle ScholarPubMed
27.Hsieh, CL, Bowcock, AM, Farrer, LAet al. The serotonin receptor subtype 2 locus HTR2 is on human chromosome 13 near genes for esterase D and retinoblastoma-1 and on mouse chromosome 14. Somat Cell Mol Genet 1990;16:567–574.CrossRefGoogle ScholarPubMed
28.Arranz, MJ, Erdmann, J, Kirov, Get al. 5-HT2A receptor and bipolar affective disorder: association studies in affected patients. Neurosci Lett 1997;224:95–98.CrossRefGoogle ScholarPubMed
29.Gutiérrez, J, Bertranpetit, J, Collier, Det al. Genetic variation of the 5-HT2A receptor gene and bipolar affective disorder. Hum Genet 1997;100:582–584.Google ScholarPubMed
30.Etain, B, Angela, R, Isabelle Roy, CHet al. Lack of association between 5HT2A receptor gene haplotype, bipolar disorder and its clinical subtypes in a West European sample. Am J Med Genet B (Neuropsychiatr Genet) 2004;129B:29–33.CrossRefGoogle Scholar
31.Ghosh, S, Sanjeev, J, Kiran Kumar, HB, Nithin Krishna, OM, Purushottam, M. Identification of interaction between serotonin transporter and glycogen synthase kinase-3β gene polymorphisms: role in susceptibility to bipolar disorder. Future Neurol 2009;4:363–370.Google Scholar
32.Ranade, SS, Hader, M, Joel, Wet al. Linkage and association between serotonin 2A receptor gene polymorphisms and bipolar I disorder. Am J Med Genet B Neuropsychiatr Genet 2003;121B:28–34.CrossRefGoogle ScholarPubMed
33.Kumar, HB, Purushottam, M, Kubendran, Set al. Serotonergic candidate genes and puerperal psychosis: an association study. Psychiatr Genet 2007;17:253–260.CrossRefGoogle ScholarPubMed
34.Egger, M, Davey Smith, G, Schneider, M, Minder, C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–634.CrossRefGoogle ScholarPubMed
35.Arranz, MJ, Li, T, Munro, Jet al. Lack of association between a polymorphism in the promoter region of the dopamine-2 receptor gene and clozapine response. Pharmacogenetics 1998;8:481–484.CrossRefGoogle ScholarPubMed
36.Arranz, MJ, Collier, DA, Munro, Jet al. Analysis of a structural polymorphism in the 5-HT2A receptor and clinical response to clozapine. Neurosci Lett 1996;217:177–178.CrossRefGoogle ScholarPubMed
37.Melkersson, K, Hulting, AL. Serotonin receptor 2A gene polymorphisms and schizophrenia: association with family history, diagnostic subtype and height in patients. Neuro Endocrinol Lett 2009;30:343–351.Google ScholarPubMed
38.Sanders, AR, Duan, J, Levinson, DFet al. No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics. Am J Psychiatry 2008;165:497–506.CrossRefGoogle Scholar
39.Dominguez, E, Loza, MI, Padin, Fet al. Extensive linkage disequilibrium mapping at HTR2A and DRD3 for schizophrenia susceptibility genes in the Galician population. Schizophr Res 2007;90:123–129.CrossRefGoogle ScholarPubMed
40.Mata, I, Arranz, MJ, Patino, Aet al. Serotonergic polymorphisms and psychotic disorders in populations from North Spain. Am J Med Genet B Neuropsychiatr Genet 2004;126B:88–94.CrossRefGoogle ScholarPubMed
41.Segman, RH, Heresco-Levy, U, Finkel, Bet al. Association between the serotonin 2A receptor gene and tardive dyskinesia in chronic schizophrenia. Mol Psychiatry 2001;6:225–229.CrossRefGoogle ScholarPubMed
42.Kawanishi, C, Hanihara, T, Shimoda, Yet al. Lack of association between neuroleptic malignant syndrome and polymorphisms in the 5-HT1A and 5-HT2A receptor genes. Am J Psychiatry 1998;155:1275–1277.CrossRefGoogle ScholarPubMed
43.Erdmann, J, Shimron-Abarbanell, D, Rietschel, Met al. Systematic screening for mutations in the human serotonin-2A (5-HT2A) receptor gene: identification of two naturally occurring receptor variants and association analysis in schizophrenia. Hum Genet 1996;97:614–619.CrossRefGoogle ScholarPubMed
44.Akiskal, HS. Validating ‘hard’ and ‘soft’ phenotypes within the bipolar spectrum: continuity or discontinuity? J Affect Disord 2003;73:1–5.CrossRefGoogle ScholarPubMed
45.Judd, LL, Akiskal, HS, Schettler, PJet al. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry 2003;60:261–269.CrossRefGoogle ScholarPubMed
46.McMahon, FJ, Simpson, SG, McInnis, MG, Badner, JA, MacKinnon, DF, DePaulo, JR. Linkage of bipolar disorder to chromosome 18q and the validity of bipolar II disorder. Arch Gen Psychiatry 2001;58:1025–1031.CrossRefGoogle ScholarPubMed
47.Lee, SY, Chen, SL, Chang, YHet al. The ALDH2 and 5-HT2A genes interacted in bipolar-I but not bipolar-II disorder. Prog Neuropsychopharmacol Biol Psychiatry 2012;38:247–251.CrossRefGoogle Scholar