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BMC Psychiatry
Published in: BMC Psychiatry 1/2013

Open Access 01-12-2013 | Research article

Association of the 5HTR2A gene with suicidal behavior: CASE-control study and updated meta-analysis

Authors: Thelma Beatriz González-Castro, Carlos Tovilla-Zárate, Isela Juárez-Rojop, Sherezada Pool García, Martha Patricia Velázquez-Sánchez, Alma Genis, Humberto Nicolini, Lilia López Narváez

Published in: BMC Psychiatry | Issue 1/2013

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Abstract

Background

The polymorphism rs6313 (T102C) has been associated with suicidal behavior in case–control and meta-analysis studies, but results and conclusions remain controversial. The aim of the present study was to examine the association between T102C with suicidal behavior in a case–control study and, to assess the combined evidence – this case–control study and available data from other related studies – we carried out a meta-analysis.

Methods

We conducted a case–control study that included 161 patients with suicide attempts and 244 controls; we then performed a meta-analysis. The following models were evaluated in the meta-analysis: A) C allele vs T allele; B) T allele vs C allele; C) Caucasian population, D) Asian population, and E) suicide attempters with schizophrenia.

Results

We found an association between attempted suicide and control participants for genotype (χ2=6.28, p=0.04, df=2) and allele (χ2=6.17, p=0.01, df=1, OR 1.48 95% IC: 1.08-2.03) frequencies in the case–control study. The meta-analysis, comprising 23 association studies (including the present one), showed that the rs6313 polymorphism is not associated with suicidal behavior for the following comparisons:T allele vs C allele (OR: 1.03; 95% CI 0.93-1.13; p(Z)=0.44); C allele vs T allele: (OR:0.99; 95% CI: 0.90-1.08; p(Z)=0.22); Caucasians (OR:1.09; 95% CI: 0.96-1.23), and Asians (OR:0.96; 95% CI: 0.84-1.09).

Conclusion

Our results showed association between the rs6313 (T102C) polymorphism and suicidal behavior in the case–control study. However, the meta-analysis showed no evidence of association. Therefore, more studies are necessary to determine conclusively an association between T102C and suicidal behavior.
Appendix
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Literature
1.
Murphy TM, Ryan M, Foster T, Kelly C, McClelland R, O'Grady J, Corcoran E, Brady J, Reilly M, Jeffers A, et al: Risk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms. Behav Brain Funct. 2011, 7: 22-10.1186/1744-9081-7-22.CrossRefPubMedPubMedCentral
2.
Tovilla-Zarate C, Juarez-Rojop I, Ramon-Frias T, Villar-Soto M, Pool-Garcia S, Medellin BC, Genis Mendoza AD, Narvaez LL, Humberto N: No association between COMT val158met polymorphism and suicidal behavior: meta-analysis and new data. BMC Psychiatry. 2011, 11: 151-10.1186/1471-244X-11-151.CrossRefPubMedPubMedCentral
3.
Roy A, Agren H, Pickar D, Linnoila M, Doran AR, Cutler NR, Paul SM: Reduced CSF concentrations of homovanillic acid and homovanillic acid to 5-hydroxyindoleacetic acid ratios in depressed patients: relationship to suicidal behavior and dexamethasone nonsuppression. Am J Psychiatry. 1986, 143 (12): 1539-1545.CrossRefPubMed
4.
Traskman L, Asberg M, Bertilsson L, Sjostrand L: Monoamine metabolites in CSF and suicidal behavior. Arch Gen Psychiatry. 1981, 38 (6): 631-636. 10.1001/archpsyc.1981.01780310031002.CrossRefPubMed
5.
Asberg M, Traskman L, Thoren P: 5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor?. Arch Gen Psychiatry. 1976, 33 (10): 1193-1197. 10.1001/archpsyc.1976.01770100055005.CrossRefPubMed
6.
Savitz JB, Cupido CL, Ramesar RS: Trends in suicidology: personality as an endophenotype for molecular genetic investigations. PLoS Med. 2006, 3 (5): e107-10.1371/journal.pmed.0030107.CrossRefPubMedPubMedCentral
7.
Angles MR, Ocana DB, Medellin BC, Tovilla-Zarate C: No association between the HTR1A gene and suicidal behavior: a meta-analysis. Rev Bras Psiquiatr. 2012, 34 (1): 38-42.CrossRefPubMed
8.
Saiz PA, Garcia-Portilla P, Paredes B, Corcoran P, Arango C, Morales B, Sotomayor E, Alvarez V, Coto E, Florez G, et al: Role of serotonergic-related systems in suicidal behavior: Data from a case–control association study. Prog Neuropsychopharmacol Biol Psychiatry. 2011, 35 (6): 1518-1524. 10.1016/j.pnpbp.2011.04.011.CrossRefPubMed
9.
Mann JJ, Arango VA, Avenevoli S, Brent DA, Champagne FA, Clayton P, Currier D, Dougherty DM, Haghighi F, Hodge SE, et al: Candidate endophenotypes for genetic studies of suicidal behavior. Biol Psychiatry. 2009, 65 (7): 556-563. 10.1016/j.biopsych.2008.11.021.CrossRefPubMedPubMedCentral
10.
Benko A, Lazary J, Molnar E, Gonda X, Tothfalusi L, Pap D, Mirnics Z, Kurimay T, Chase D, Juhasz G, et al: Significant association between the C(−1019)G functional polymorphism of the HTR1A gene and impulsivity. Am J Med Genet B Neuropsychiatr Genet. 2010, 153B (2): 592-599.PubMed
11.
Zalsman GIL, Patya M, Frisch A, Ofek H, Schapir L, Blum I, Harell D, Apter A, Weizman A, Tyano S: Association of polymorphisms of the serotonergic pathways with clinical traits of impulsive-aggression and suicidality in adolescents: A multi-center study. World J Biol Psychiatry. 2011, 12 (1): 33-41. 10.3109/15622975.2010.518628.CrossRefPubMed
12.
Vang FJ, Lindstrom M, Sunnqvist C, Bah-Rosman J, Johanson A, Traskman-Bendz L: Life-time adversities, reported thirteen years after a suicide attempt: relationship to recovery, 5HTTLPR genotype, and past and present morbidity. Arch Suicide Res. 2009, 13 (3): 214-229. 10.1080/13811110903044328.CrossRefPubMed
13.
Yoon HK, Kim YK: TPH2–703G/T SNP may have important effect on susceptibility to suicidal behavior in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2009, 33 (3): 403-409. 10.1016/j.pnpbp.2008.12.013.CrossRefPubMed
14.
Turecki G, Briere R, Dewar K, Antonetti T, Lesage AD, Seguin M, Chawky N, Vanier C, Alda M, Joober R, et al: Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide. Am J Psychiatry. 1999, 156 (9): 1456-1458.PubMed
15.
Norton N, Owen MJ: HTR2A: association and expression studies in neuropsychiatric genetics. Ann Med. 2005, 37 (2): 121-129. 10.1080/07853890510037347.CrossRefPubMed
16.
Ben-Efraim YJ, Wasserman D, Wasserman J, Sokolowski M: Family-based study of HTR2A in suicide attempts: observed gene, gene x environment and parent-of-origin associations. Mol Psychiatry. 2012, 3 (10): 86-
17.
Correa H, De Marco L, Boson W, Viana MM, Lima VF, Campi-Azevedo AC, Noronha JC, Guatimosim C, Romano-Silva MA: Analysis of T102C 5HT2A polymorphism in Brazilian psychiatric inpatients: relationship with suicidal behavior. Cell Mol Neurobiol. 2002, 22 (5–6): 813-817.CrossRefPubMed
18.
Etain B, Rousseva A, Roy I, Henry C, Malafosse A, Buresi C, Preisig M, Rayah F, Leboyer M, Bellivier F: 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, 15 (1): 29-33.CrossRef
19.
Correa H, Nicolata R, Teixeira A, De Marco LA, Romano-Silva MA: Association study of the T102C 5-HT2A polymorphism in schizophrenia: Diagnosis, psychopathology ans suicidal behavior. Am J Med Genet B Neuropsychiatr Genet. 2006, 141B (7): 802-802.
20.
Ertugrul A, Kennedy JL, Masellis M, Basile VS, Jayathilake K, Meltzer HY: No association of the T102C polymorphism of the serotonin 2A receptor gene (HTR2A) with suicidality in schizophrenia. Schizophr Res. 2004, 69 (2–3): 301-305.CrossRefPubMed
21.
Correa H, De Marco L, Boson W, Nicolato R, Teixeira AL, Campo VR, Romano-Silva MA: Association study of T102C 5-HT(2A) polymorphism in schizophrenic patients: diagnosis, psychopathology, and suicidal behavior. Dialogues Clin Neurosci. 2007, 9 (1): 97-101.PubMedPubMedCentral
22.
Wrzosek M, Lukaszkiewicz J, Serafin P, Jakubczyk A, Klimkiewicz A, Matsumoto H, Brower KJ, Wojnar M: Association of polymorphisms in HTR2A, HTR1A and TPH2 genes with suicide attempts in alcohol dependence: a preliminary report. Psychiatry Res. 2011, 190 (1): 149-151. 10.1016/j.psychres.2011.04.027.CrossRefPubMedPubMedCentral
23.
Khait VD, Huang YY, Zalsman G, Oquendo MA, Brent DA, Harkavy-Friedman JM, Mann JJ: Association of serotonin 5-HT2A receptor binding and the T102C polymorphism in depressed and healthy Caucasian subjects. Neuropsychopharmacology. 2005, 30 (1): 166-172. 10.1038/sj.npp.1300578.CrossRefPubMed
24.
25.
Beck AT, Kovacs M, Weissman A: Assessment of suicidal intention: the Scale for Suicide Ideation. J Consult Clin Psychol. 1979, 47 (2): 343-352.CrossRefPubMed
26.
Lahiri DK, Nurnberger JI: A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res. 1991, 19 (19): 5444-10.1093/nar/19.19.5444.CrossRefPubMedPubMedCentral
27.
Swartz MK: The PRISMA statement: a guideline for systematic reviews and meta-analyses. J Pediatr Health Care. 2011, 25 (1): 1-2. 10.1016/j.pedhc.2010.09.006.CrossRefPubMed
28.
Tovilla-Zarate C, Camarena B, Apiquian R, Nicolini H: Association study and meta-analysis of the apolipoprotein gene and schizophrenia. Gac Med Mex. 2008, 144 (2): 79-83.PubMed
29.
Kavvoura FK, Ioannidis JP: Methods for meta-analysis in genetic association studies: a review of their potential and pitfalls. Hum Genet. 2008, 123 (1): 1-14. 10.1007/s00439-007-0445-9.CrossRefPubMed
30.
Du L, Bakish D, Lapierre YD, Ravindran AV, Hrdina PD: Association of polymorphism of serotonin 2A receptor gene with suicidal ideation in major depressive disorder. Am J Med Genet. 2000, 96 (1): 56-60. 10.1002/(SICI)1096-8628(20000207)96:1<56::AID-AJMG12>3.0.CO;2-L.CrossRefPubMed
31.
Vaquero-Lorenzo C, Baca-Garcia E, Diaz-Hernandez M, Perez-Rodriguez MM, Fernandez-Navarro P, Giner L, Carballo JJ, Saiz-Ruiz J, Fernandez-Piqueras J, Baldomero EB, et al: Association study of two polymorphisms of the serotonin-2A receptor gene and suicide attempts. Am J Med Genet B Neuropsychiatr Genet. 2008, 147B (5): 645-649. 10.1002/ajmg.b.30642.CrossRefPubMed
32.
Bondy B, Kuznik J, Baghai T, Schule C, Zwanzger P, Minov C, de Jonge S, Rupprecht R, Meyer H, Engel RR, et al: Lack of association of serotonin-2A receptor gene polymorphism (T102C) with suicidal ideation and suicide. Am J Med Genet. 2000, 96 (6): 831-835. 10.1002/1096-8628(20001204)96:6<831::AID-AJMG27>3.0.CO;2-K.CrossRefPubMed
33.
Arias B, Gasto C, Catalan R, Gutierrez B, Pintor L, Fananas L: The 5-HT(2A) receptor gene 102T/C polymorphism is associated with suicidal behavior in depressed patients. Am J Med Genet. 2001, 105 (8): 801-804. 10.1002/ajmg.10099.CrossRefPubMed
34.
Tsai SJ, Hong CJ, Hsu CC, Cheng CY, Liao WY, Song HL, Lai HC: Serotonin-2A receptor polymorphism (102T/C) in mood disorders. Psychiatry Res. 1999, 87 (2–3): 233-237.CrossRefPubMed
35.
Crawford J, Sutherland GR, Goldney RD: No evidence for association of 5-HT2A receptor polymorphism with suicide. Am J Med Genet. 2000, 96 (6): 879-880. 10.1002/1096-8628(20001204)96:6<879::AID-AJMG39>3.0.CO;2-M.CrossRefPubMed
36.
Saiz PA, Garcia-Portilla MP, Paredes B, Arango C, Morales B, Alvarez V, Coto E, Bascaran MT, Bousono M, Bobes J: Association between the A-1438G polymorphism of the serotonin 2A receptor gene and nonimpulsive suicide attempts. Psychiatr Genet. 2008, 18 (5): 213-218. 10.1097/YPG.0b013e3283050ada.CrossRefPubMed
37.
Preuss UW, Koller G, Bahlmann M, Soyka M, Bondy B: No association between suicidal behavior and 5-HT2A-T102C polymorphism in alcohol dependents. Am J Med Genet. 2000, 96 (6): 877-878. 10.1002/1096-8628(20001204)96:6<877::AID-AJMG38>3.0.CO;2-V.CrossRefPubMed
38.
Zhang J, Shen Y, He G, Li X, Meng J, Guo S, Li H, Gu N, Feng G, He L: Lack of association between three serotonin genes and suicidal behavior in Chinese psychiatric patients. Prog Neuropsychopharmacol Biol Psychiatry. 2008, 32 (2): 467-471. 10.1016/j.pnpbp.2007.09.019.CrossRefPubMed
39.
Ono H, Shirakawa O, Nishiguchi N, Nishimura A, Nushida H, Ueno Y, Maeda K: Serotonin 2A receptor gene polymorphism is not associated with completed suicide. J Psychiatr Res. 2001, 35: 173-176. 10.1016/S0022-3956(01)00015-2.CrossRefPubMed
40.
Du L, Faludi G, Palkovits M, Demeter E, Bakish D, Lapierre YD, Sotonyi P, Hrdina PD: Frequency of long allele in serotonin transporter gene is increased in depressed suicide victims. Biol Psychiatry. 1999, 46 (2): 196-201. 10.1016/S0006-3223(98)00376-X.CrossRefPubMed
41.
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 Biophys Res Commun. 2006, 340 (3): 1006-1015. 10.1016/j.bbrc.2005.12.101.CrossRefPubMed
42.
Paredes B, Alejandra SP, Paz G-PM, Morales B, Mercedes P, Fernandez I, Ivan G, Victoria A, Eliecer C, María B, et al: Asociación entre el polimorfismo A-1438G del gen del receptor de serotonina 2A (5HT2A) e impulsividad del comportamiento suicida. Emergencias. 2008, 20: 93-100.
43.
Ono H, Shirakawa O, Nishiguchi N, Nishimura A, Nushida H, Ueno Y, Maeda K: Serotonin 2A receptor gene polymorphism is not associated with completed suicide. J Psychiatr Res. 2001, 35 (3): 173-176. 10.1016/S0022-3956(01)00015-2.CrossRefPubMed
44.
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 (1): 53-62. 10.1016/S0920-9964(03)00183-X.CrossRefPubMed
45.
Anguelova M, Benkelfat C, Turecki G: A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: II. Suicidal behavior. Mol Psychiatry. 2003, 8 (7): 646-653. 10.1038/sj.mp.4001336.CrossRefPubMed
46.
Forero DA, Arboleda GH, Vasquez R, Arboleda H: Candidate genes involved in neural plasticity and the risk for attention-deficit hyperactivity disorder: a meta-analysis of 8 common variants. J Psychiatry Neurosci. 2009, 34 (5): 361-366.PubMedPubMedCentral
Metadata
Title
Association of the 5HTR2A gene with suicidal behavior: CASE-control study and updated meta-analysis
Authors
Thelma Beatriz González-Castro
Carlos Tovilla-Zárate
Isela Juárez-Rojop
Sherezada Pool García
Martha Patricia Velázquez-Sánchez
Alma Genis
Humberto Nicolini
Lilia López Narváez
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-13-25

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