Hostname: page-component-cd9895bd7-7cvxr Total loading time: 0 Render date: 2024-12-22T11:56:35.517Z Has data issue: false hasContentIssue false
  • English
  • Français

Association of schizophrenia with T102C (rs6313) and 1438 A/G (rs6311) polymorphisms of HTR2A gene

Published online by Cambridge University Press:  29 May 2013

Saliha Handan Yildiz ,
Asli Akilli ,
Erman Bagcioglu ,
Mujgan Ozdemir Erdogan ,
Kerem Senol Coskun ,
Ahmet Hamdi Alpaslan ,
Burak Subasi  and
Evrim Suna Arikan Terzi
Saliha Handan Yildiz*
Affiliation:
Department of Medical Genetics, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey
Asli Akilli
Affiliation:
Department of Medical Genetics, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey
Erman Bagcioglu
Affiliation:
Department of Psychiatry, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey
Mujgan Ozdemir Erdogan
Affiliation:
Department of Medical Genetics, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey
Kerem Senol Coskun
Affiliation:
Department of Psychiatry, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey
Ahmet Hamdi Alpaslan
Affiliation:
Department of Psychiatry, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey
Burak Subasi
Affiliation:
Elazıg Training and Research Hospital, Elazıg, Turkey
Evrim Suna Arikan Terzi
Affiliation:
Department of Medical Genetics, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey
*
Dr. Saliha Handan Yildiz, Department of Medical Genetic, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey. Tel: +90-505 5044162; Fax: +90-272 2463300; E-mail: handanstarr@gmail.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

The aim of this study is to investigate whether there were any associations between the T102C and 1438 A/G polymorphisms of the 5-HT2A receptor gene and schizophrenia. We conducted a case–control study of the T102C and 1438 A/G polymorphisms in Turkish patients.

Methods

We compared genotypes and allele frequencies of T102C and 1438 A/G polymorphisms of 5-HT2A receptor gene in 102 patients with schizophrenia diagnosed, according to DSM-IV, and 107 healthy controls. Genotyping was performed by real-time polymerase chain reaction.

Results

We found no significant association between schizophrenia and genotypic or allele frequencies of HTR2A gene 102T/C (rs6313) and 1438 A/G (6311) polymorphisms. However, comparison of HTR2A gene 102 T/C and 1438 A/G polymorphisms in terms of genotypic and allele frequencies between the two patient groups, with or without a family history of schizophrenia, shows that T- and A-allele frequencies were significantly higher (p < 0.05) in the case group that has a history of schizophrenia in their family.

Conclusion

In conclusion, our results do not support the hypothesis that the T102C and 1438 A/G polymorphisms in the 5-HT2A receptor gene are associated with schizophrenia, but further studies in a larger sample are needed.

Keywords

HTR2ApolymorphismschizophreniaT102C1438 A/G
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 25 , Issue 6 , December 2013 , pp. 342 - 348
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Vaquero Lorenzo, C, Baca-Garcia, E, Diaz-Hernandez, Met al. Association between the T102C polymorphism of the serotonin-2A receptor gene and schizophrenia. Prog Neuro-Psychoph 2006;30:1136–1138.CrossRefGoogle ScholarPubMed
2.Schwab, SG, Wildenauer, DB. Research on causes for schizophrenia: are we close? Schizophr Res 2008;102:29–30.CrossRefGoogle ScholarPubMed
3.Owen, MJ, Craddock, N, O'donovan, MC. Schizophrenia: genes at last? Trends Genet 2005;21:518–525.CrossRefGoogle ScholarPubMed
4.Roth, BL, Meltzer, HY. The role of serotonin in schizophrenia. In: Bloom FE and Kupfer DJ, eds. Psychopharmacology. The fourth generation of progress. New York: Raven Press, 1995:1215–1228.Google Scholar
5.Tee, SF, Chow, TJ, Tang, PY, Loh, HC. Linkage of schizophrenia with TPH2 and 5-HTR2A gene polymorphisms in the Malay population. Genet Mol Res 2010;9:1274–1278.CrossRefGoogle ScholarPubMed
6.Sáiz, PA, Garcia-Portilla, MP, Arango, Cet al. Association study of serotonin 2A receptor (5-HT2A) and serotonin transporter (5-HTT) gene polymorphisms with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:741–745.CrossRefGoogle ScholarPubMed
7.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 Cel Molec Gen 1990;16:567–574.CrossRefGoogle ScholarPubMed
8.Chen, K, Yang, W, Grimsby, J, Shih, JC. The human 5-HT2 receptor is encoded by a multiple intron-exon gene. Brain Res Mol Brain Res 1992;14:20–26.CrossRefGoogle ScholarPubMed
9.Prasad, S, Semwal, P, Deshpande, S, Bhatia, T, Nimgaonkar, VL, Thelma, BK. Molecular genetics of schizophrenia: past, present and future. J Biosci 2002;27:35–52.CrossRefGoogle ScholarPubMed
10.Hernandez, I, Sokolov, BP. Abnormalities in 5-HT2A receptor mRNA expression in frontal cortex of chronic elderly schizophrenics with varying histories of neuroleptic treatment. J Neurosci Res 2000;59:218–225.3.0.CO;2-H>CrossRefGoogle ScholarPubMed
11.Matsumoto, I, Inoue, Y, Iwazaki, T, Pavey, G, Dean, B. 5-HT2A and muscarinic receptors in schizophrenia: a postmortem study. Neurosci Lett 2005;379:164–168.CrossRefGoogle ScholarPubMed
12.Burnet, PW, Eastwood, SL, Harrison, PJ. 5-HT1A and 5-HT2A receptor mRNAs and binding site densities are differentially altered in schizophrenia. Neuropsychopharmacoly 1996;15:442–455.CrossRefGoogle ScholarPubMed
13.Ohara, K, Ino, A, Ishigaki, Tet al. Analysis of the 59-flanking promoter region of the 5HT2A receptor gene in schizophrenia. Neuropsychopharmacoly 1997;17:274–278.CrossRefGoogle Scholar
14.Spurlock, G, Heils, A, Holmans, Pet al. A family based association study of T102C polymorphism in 5HT2A and schizophrenia plus identification of new polymorphisms in the promoter. Mol Psychiatry 1998;3:42–49.CrossRefGoogle ScholarPubMed
15.Souery, D, Oswald, P, Linkowski, P, Mendlewicz, J. Molecular genetics in the analysis of suicide. Ann Med 2003;35:191–196.CrossRefGoogle ScholarPubMed
16.Du, L, Faludi, G, Palkovits, M, Bakish, D, Hrdina, PD. Serotonergic genes and suicidality. Crisis 2001;22:54–60.CrossRefGoogle ScholarPubMed
17.Virgos, C, Martorell, L, Valero, Jet al. Association study of schizophrenia with polymorphisms at six candidate genes. Schizophr Res 2001;49:65–71.CrossRefGoogle ScholarPubMed
18.Abdolmaleky, HM, Faraone, SV, Glatt, SJ, Tsuang, MT. Meta-analysis of association between the T102C polymorphism of the 5HT2a receptor gene and schizophrenia. Schizophr Res 2004;67:53–62.CrossRefGoogle ScholarPubMed
19.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
20.Williams, J, Spurlock, G, Mcguffin, Pet al. Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene. Lancet 1996;347:1294–1296.CrossRefGoogle ScholarPubMed
21.Baritaki, S, Rizos, E, Zafiropoulos, Aet al. Association between schizophrenia and DRD3 or HTR2 receptor gene variants. Eur J Hum Genet 2004;12:535–541.CrossRefGoogle ScholarPubMed
22.Warren, JT Jr, Peacock, ML, Rodriguez, LC, Fink, JK. An MspI polymorphism in the human serotonin receptor gene (HTR2): detection by DGGE and RFLP analysis. Hum Mol Genet 1993;2:338.CrossRefGoogle ScholarPubMed
23.Nimgaonkar, VL, Zhang, XR, Brar, JS, Deleo, M, Ganguli, R. 5HT2 receptor gene locus: association with schizophrenia or treatment response not detected. Psychiat Genet 1996;6:23–27.CrossRefGoogle Scholar
24.Hawi, Z, Myakishev, MV, Straub, REet al. No association or linkage between the 5-HT2arT102C polymorphism and schizophrenia in Irish families. Am J Med Genet 1997;25:370–373.3.0.CO;2-T>CrossRefGoogle Scholar
25.Collier, DA, Arranz, MJ, Li, T, Mupita, D, Brown, N, Treasure, J. Association between 5-HT2A gene promoter polymorphism and anorexia nervosa. Lancet 1997;350:412.CrossRefGoogle ScholarPubMed
26.Gu, L, Long, J, Yan, Yet al. HTR2A-1438A/G polymorphism influences the risk of schizophrenia but not bipolar disorder or major depressive disorder: a meta-analysis. J Neurosci Res 2013;91:623–633.CrossRefGoogle ScholarPubMed
27.Li, D, Duan, Y, He, L. Association study of serotonin 2A receptor (5-HT2A) gene with schizophrenia and suicidal behavior using systematic meta-analysis. Biochem Bioph Res Co 2006;340:1006–1015.CrossRefGoogle ScholarPubMed
28.Fan, JB, Sklar, P. Meta-analysis reveals association between serotonin transporter gene Stin2 VNTR polymorphism and schizophrenia. Mol Psychiatry 2005;10:928–938.CrossRefGoogle ScholarPubMed
29.Williams, J, Mcguffin, P, Nothen, M, Owen, MJ. Meta-analysis of association between the 5-HT2A receptor T102C polymorphism and schizophrenia. Lancet 1997;349:1221.CrossRefGoogle ScholarPubMed
30.Serretti, A, Drago, A, De Ronchi, D. HTR2A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies. Curr Med Chem 2007;14:2053–2069.Google ScholarPubMed
31.Collins, AL, Kim, Y, Sklar, P. International Schizophrenia Consortium, O'Donovan MC, Sullivan PF. Hypothesis-driven candidate genes for schizophrenia compared to genome-wide association results. Psychol Med 2012;42:607–616.CrossRefGoogle ScholarPubMed
32.Galaktionova, DI, Gra, OA, Nizamutdinov, IIet al. An association study of polymorphisms in HTR2A, BDNF and SLC6A4 genes with paranoid schizophrenia and suicidal behavior. Zh Nevrol Psikhiatr Im S S Korsakova 2012;112:39–44.Google ScholarPubMed
33.Herken, H, Erdal, ME, Erdal, N, Aynacioglu, S. T102C polymorphisms at the 5-HT2A receptor gene in Turkish schizophrenia patients: a possible association with prognosis. Neuropsychobiology 2003;47:27–30.CrossRefGoogle ScholarPubMed
34.Golimbet, VE, Lavrushina, OM, Kaleda, VG, Abramova, LI, Lezheiko, TV. Supportive evidence for the association between the T102C 5-HTR2A gene polymorphism and schizophrenia: a large-scale case-control and family-based study. Eur Psychiat 2007;22:167–170.CrossRefGoogle ScholarPubMed
35.Polesskaya, OO, Sokolov, BP. Differential expression of the ‘C’ and ‘T’ alleles of the 5-HT2A receptor gene in the temporal cortex of normal individuals and schizophrenics. J Neurosci Res 2002;67:812–822.CrossRefGoogle Scholar
36.Schultz, SH, North, SW, Shields, CG. Schizophrenia: a review. Am Fam Physician 2007;75:1821–1830.Google ScholarPubMed
37.Prasad, KM, Talkowski, ME, Chowdari, KVet al. Candidate genes and their interactions with other genetic/environmental risk factors in the etiology of schizophrenia. Brain Res Bull 2010;83:86–92.CrossRefGoogle ScholarPubMed
38.Kendler, KS, Diehl, SR. The genetics of schizophrenia: a current, genetic-epidemiologic perspective. Schizophr Bull 1993;19:261–285.CrossRefGoogle ScholarPubMed
39.Mcguffin, P, Owen, MJ, Farmer, AE. Genetic basis of schizophrenia. Lancet 1995;346:678–682.CrossRefGoogle ScholarPubMed
40.Chen, RYL, Sham, P, Chena, EYHet al. No association between T102C polymorphism of serotonin-2A receptor gene and clinical phenotypes of Chinese schizophrenic patients. Psychiatry Res 2001;105:175–185.CrossRefGoogle ScholarPubMed
41.Tay, AH, Lim, LC, Lee, WL, Wong, KE, Wong, LY, Tsoi, WF. Association between allele 1 of T102C polymorphism, 5-hydroxytryptamine 2a receptor gene and schizophrenia in Chinese males in Singapore. Hum Hered 1997;47:298–300.CrossRefGoogle ScholarPubMed
42.Ozgur Gunes, S, Boke, O, Kara, N, Sahin, AR, Bagci, H, Basar, Y. Sizofreni hastalarında 5-HT2A reseptörü geni -1438 G/A polimorfizminin incelenmesi. Anadolu Psikiyatr De 2006;7:13–17.Google Scholar
43.Kim, YK, Yoon, HK. Effect of serotonin-related gene polymorphisms on pathogenesis and treatment response in Korean schizophrenic patients. Behav Genet 2011;41:709–715.CrossRefGoogle ScholarPubMed
44.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
45.Tsuang, HC, Chen, WJ, Lin, SHet al. Impaired impulse control is associated with a 5-HT2A receptor polymorphism in schizophrenia. Psychiatry Res 2012, Doi:10.1016/j.psychres.2012.09.038.Google ScholarPubMed