Polymorphisms in the Regulatory Region of the Human Serotonin 5-HT2A Receptor Gene (HTR2A) Influence Gene Expression

Biological Psychiatry

Volumn 61, Issue 2, 2007, Pages 167-173

  Myers, Regina L ^a   Airey, David C ^a   Manier, D Hal ^a   Shelton, Richard C ^a   Sanders Bush, Elaine ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

5 HT2A receptor; Gene expression; genetics; polymorphism; serotonin; SNP

Indexed keywords

LUCIFERASE; MESSENGER RNA; SEROTONIN 2A RECEPTOR;

ADULT; ALLELE; ARTICLE; CONTROLLED STUDY; ENZYME ASSAY; EPISTASIS; EX VIVO STUDY; FEMALE; FIBROBLAST; GENE EXPRESSION; GENE FREQUENCY; GENE FUNCTION; GENE LINKAGE DISEQUILIBRIUM; GENE LOCUS; HUMAN; HUMAN CELL; IN VITRO STUDY; MALE; MENTAL DISEASE; PRIORITY JOURNAL; PROMOTER REGION; REAL TIME POLYMERASE CHAIN REACTION; RECEPTOR GENE; REGULATOR GENE; SINGLE NUCLEOTIDE POLYMORPHISM; STATISTICAL SIGNIFICANCE;

ADULT; EPISTASIS, GENETIC; FEMALE; GENE EXPRESSION; GENE FREQUENCY; GENOTYPE; HUMANS; LINKAGE DISEQUILIBRIUM; MALE; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; PROMOTER REGIONS (GENETICS); RECEPTOR, SEROTONIN, 5-HT2A; REGULATORY SEQUENCES, NUCLEIC ACID; RNA, MESSENGER;

EID: 33846088587     PISSN: 00063223     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.biopsych.2005.12.018     Document Type: Article

References (53)

1. Abdolmaleky H.M., Faraone S.V., Glatt S.J., and Tsuang M.T. Meta-analysis of association between the T102C polymorphism of the 5HT2a receptor gene and schizophrenia. Schizophr Res 67 (2004) 53-62
2. Akin D., Manier D.H., Sanders-Bush E., and Shelton R.C. Decreased serotonin 5-HT(2A) receptor-stimulated phosphoinositide signaling in fibroblasts from melancholic depressed patients. Neuropsychopharmacology 29 (2004) 2081-2087
3. Arango V., Ernsberger P., Marzuk P.M., Chen J.S., Tierney H., Stanley M., et al. Autoradiographic demonstration of increased serotonin 5-HT2 and beta-adrenergic receptor binding sites in the brain of suicide victims. Arch Gen Psychiatry 47 (1990) 1038-1047
4. Arora R.C., and Meltzer H.Y. Increased serotonin2 (5-HT2) receptor binding as measured by 3H-lysergic acid diethylamide (3H-LSD) in the blood platelets of depressed patients. Life Sci 44 (1989) 725-734
5. Arora R.C., and Meltzer H.Y. Serotonergic measures in the brains of suicide victims: 5-HT2 binding sites in the frontal cortex of suicide victims and control subjects. Am J Psychiatry 146 (1989) 730-736
6. Bondy B., Kuznik J., Baghai T., Schule C., Zwanzger P., Minov C., et al. Lack of association of serotonin-2A receptor gene polymorphism (T102C) with suicidal ideation and suicide. Am J Med Genet 96 (2000) 831-835
7. Bray N.J., Buckland P.R., Hall H., Owen M.J., and O'Donovan M.C. The serotonin-2A receptor gene locus does not contain common polymorphism affecting mRNA levels in adult brain. Mol Psychiatry 9 (2004) 109-114
8. Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., et al. Characterization of single-nucleotide polymorphisms in coding regions of human genes [published erratum appears in Nat Genet 1999 23(3):373]. Nat Genet 22 (1999) 231-238
9. Cheetham S.C., Crompton M.R., Katona C.L., and Horton R.W. Brain 5-HT2 receptor binding sites in depressed suicide victims. Brain Res 443 (1988) 272-280
10. Chen K., Yang W., Grimsby J., and Shih J.C. The human 5-HT2 receptor is encoded by a multiple intron-exon gene. Brain Res Mol Brain Res 14 (1992) 20-26
11. Choi M.J., Lee H.J., Ham B.J., Cha J.H., Ryu S.H., and Lee M.S. Association between major depressive disorder and the -1438A/G polymorphism of the serotonin 2A receptor gene. Neuropsychobiology 49 (2004) 38-41
12. Cleves M. Exploratory analysis of single nucleotide polymorphism (SNP) for quantitative traits. Stata J 5 (2005) 141-153
13. Cusin C., Serretti A., Zanardi R., Lattuada E., Rossini D., Lilli R., et al. Influence of monoamine oxidase A and serotonin receptor 2A polymorphisms in SSRI antidepressant activity. Int J Neuropsychopharmacol 5 (2002) 27-35
14. Du L., Faludi G., Palkovits M., Demeter E., Bakish D., Lapierre Y.D., et al. Frequency of long allele in serotonin transporter gene is increased in depressed suicide victims. Biol Psychiatry 46 (1999) 196-201
15. Elliott J.M., Newberry N.R., Cholewinski A.J., Bartrup J.T., Briddon S.J., Carey J.E., et al. Characterization of the 5-hydroxytryptamine2A receptor-activated cascade in rat C6 glioma cells. Neuroscience 69 (1995) 1119-1131
16. Frisch A., Michaelovsky E., Rockah R., Amir I., Hermesh H., Laor N., et al. Association between obsessive-compulsive disorder and polymorphisms of genes encoding components of the serotonergic and dopaminergic pathways. Eur Neuropsychopharmacol 10 (2000) 205-209
17. Frisch A., Postilnick D., Rockah R., Michaelovsky E., Postilnick S., Birman E., et al. Association of unipolar major depressive disorder with genes of the serotonergic and dopaminergic pathways. Mol Psychiatry 4 (1999) 389-392
18. Gorwood P., Ades J., Bellodi L., Cellini E., Collier D.A., Di Bella D., et al. The 5-HT(2A) -1438G/A polymorphism in anorexia nervosa: A combined analysis of 316 trios from six European centres. Mol Psychiatry 7 (2002) 90-94
19. Gross-Isseroff R., Salama D., Israeli M., and Biegon A. Autoradiographic analysis of age-dependent changes in serotonin 5-HT2 receptors of the human brain postmortem. Brain Res 519 (1990) 223-227
20. Hrdina P.D., Bakish D., Chudzik J., Ravindran A., and Lapierre Y.D. Serotonergic markers in platelets of patients with major depression: Upregulation of 5-HT2 receptors. J Psychiatry Neurosci 20 (1995) 11-19
21. Hrdina P.D., Bakish D., Ravindran A., Chudzik J., Cavazzoni P., and Lapierre Y.D. Platelet serotonergic indices in major depression: Up-regulation of 5-HT2A receptors unchanged by antidepressant treatment. Psychiatry Res 66 (1997) 73-85
22. Hrdina P.D., Demeter E., Vu T.B., Sotonyi P., and Palkovits M. 5-HT uptake sites and 5-HT2 receptors in brain of antidepressant-free suicide victims/depressives: Increase in 5-HT2 sites in cortex and amygdala. Brain Res 614 (1993) 37-44
23. Jansson M., Gatz M., Berg S., Johansson B., Malmberg B., McClearn G.E., et al. Association between depressed mood in the elderly and a 5-HTR2A gene variant. Am J Med Genet B Neuropsychiatr Genet 120 (2003) 79-84
24. Khait V.D., Huang Y.Y., Zalsman G., Oquendo M.A., Brent D.A., Harkavy-Friedman J.M., and Mann J.J. Association of serotonin 5-HT2A receptor binding and the T102C polymorphism in depressed and healthy Caucasian subjects. Neuropsychopharmacology 30 (2005) 166-172
25. Kouzmenko A.P., Hayes W.L., Pereira A.M., Dean B., Burnet P.W., and Harrison P.J. 5-HT2A receptor polymorphism and steady state receptor expression in schizophrenia. Lancet 349 (1997) 1815
26. Kouzmenko A.P., Scaffidi A., Pereira A.M., Hayes W.L., Copolov D.L., and Dean B. No correlation between A(-1438)G polymorphism in 5-HT2A receptor gene promoter and the density of frontal cortical 5-HT2A receptors in schizophrenia. Hum Hered 49 (1999) 103-105
27. Kusumi I., Suzuki K., Sasaki Y., Kameda K., Sasaki T., and Koyama T. Serotonin 5-HT(2A) receptor gene polymorphism, 5-HT(2A) receptor function and personality traits in healthy subjects: A negative study. J Affect Disord 68 (2002) 235-241
28. Lerer B., Segman R.H., Tan E.C., Basile V.S., Cavallaro R., Aschauer H.N., et al. Combined analysis of 635 patients confirms an age-related association of the serotonin 2A receptor gene with tardive dyskinesia and specificity for the non-orofacial subtype. Int J Neuropsychopharmacol 8 (2005) 411-425
29. Mander A. Haplotype analysis in population-based association studies. Stata J 1 (2001) 58-75
30. Manier D.H., Shelton R.C., Ellis T.C., Peterson C.S., Eiring A., and Sulser F. Human fibroblasts as a relevant model to study signal transduction in affective disorders. J Affect Disord 61 (2000) 51-58
31. Mann J.J., McBride P.A., Anderson G.M., and Mieczkowski T.A. Platelet and whole blood serotonin content in depressed inpatients: Correlations with acute and life-time psychopathology. Biol Psychiatry 32 (1992) 243-257
32. Mann J.J., Stanley M., McBride P.A., and McEwen B.S. Increased serotonin2 and beta-adrenergic receptor binding in the frontal cortices of suicide victims. Arch Gen Psychiatry 43 (1986) 954-959
33. McBride P.A., Brown R.P., DeMeo M., Keilp J., Mieczkowski T., and Mann J.J. The relationship of platelet 5-HT2 receptor indices to major depressive disorder, personality traits, and suicidal behavior. Biol Psychiatry 35 (1994) 295-308
34. Nocjar C., Roth B.L., and Pehek E.A. Localization of 5-HT(2A) receptors on dopamine cells in subnuclei of the midbrain A10 cell group. Neuroscience 111 (2002) 163-176
35. Pandey G.N., Dwivedi Y., Rizavi H.S., Ren X., Pandey S.C., Pesold C., et al. Higher expression of serotonin 5-HT(2A) receptors in the postmortem brains of teenage suicide victims. Am J Psychiatry 159 (2002) 419-429
36. Pandey G.N., Pandey S.C., Janicak P.G., Marks R.C., and Davis J.M. Platelet serotonin-2 receptor binding sites in depression and suicide. Biol Psychiatry 28 (1990) 215-222
37. Parsons M.J., D'Souza U.M., Arranz M.J., Kerwin R.W., and Makoff A.J. The -1438A/G polymorphism in the 5-hydroxytryptamine type 2A receptor gene affects promoter activity. Biol Psychiatry 56 (2004) 406-410
38. Pehek E.A., Nocjar C., Roth B.L., Byrd T.A., and Mabrouk O.S. Evidence for the preferential involvement of 5-HT2A serotonin receptors in stress- and drug-induced dopamine release in the rat medial prefrontal cortex. Neuropsychopharmacology 31 (2006) 265-277
39. Polesskaya O.O., and Sokolov B.P. 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 67 (2002) 812-822
40. Rosel P., Arranz B., San L., Vallejo J., Crespo J.M., Urretavizcaya M., and Navarro M.A. Altered 5-HT(2A) binding sites and second messenger inositol trisphosphate (IP(3)) levels in hippocampus but not in frontal cortex from depressed suicide victims. Psychiatry Res 99 (2000) 173-181
41. Rosel P., Arranz B., Vallejo J., Alvarez P., Menchon J.M., Palencia T., and Navarro M.A. Altered [3H]imipramine and 5-HT2 but not [3H]paroxetine binding sites in platelets from depressed patients. J Affect Disord 52 (1999) 225-233
42. Rosel P., Arranz B., Vallejo J., Oros M., Crespo J.M., Menchon J.M., and Navarro M.A. Variations in [3H]imipramine and 5-HT2A but not [3H]paroxetine binding sites in suicide brains. Psychiatry Res 82 (1998) 161-170
43. Sheline Y.I., Bardgett M.E., Jackson J.L., Newcomer J.W., and Csernansky J.G. Platelet serotonin markers and depressive symptomatology. Biol Psychiatry 37 (1995) 442-447
44. Shelton R.C., Mainer D.H., and Sulser F. cAMP-dependent protein kinase activity in major depression. Am J Psychiatry 153 (1996) 1037-1042
45. Shelton R.C., Manier D.H., Peterson C.S., Elis T.C., and Sulser F. Cyclic AMP-dependent protein kinase in subtypes of major depression and normal volunteers. Int J Neuropsychopharm 2 (1999) 187-191
46. Sparkes R.S., Lan N., Klisak I., Mohandas T., Diep A., Kojis T., et al. Assignment of a serotonin 5HT-2 receptor gene (HTR2) to human chromosome 13q14-q21 and mouse chromosome 14. Genomics 9 (1991) 461-465
47. Spurlock G., Heils A., Holmans P., Williams J., D'Souza U.M., Cardno A., et al. A family based association study of T102C polymorphism in 5HT2A and schizophrenia plus identification of new polymorphisms in the promoter. Mol Psychiatry 3 (1998) 42-49
48. Stanley M., and Mann J.J. Increased serotonin-2 binding sites in frontal cortex of suicide victims. Lancet 1 (1983) 214-216
49. Turecki G., Briere R., Dewar K., Antonetti T., Lesage A.D., Seguin M., 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 156 (1999) 1456-1458
50. Walitza S., Wewetzer C., Warnke A., Gerlach M., Geller F., Gerber G., et al. 5-HT2A promoter polymorphism -1438G/A in children and adolescents with obsessive-compulsive disorders. Mol Psychiatry 7 (2002) 1054-1057
51. Williams J., McGuffin P., Nothen M., and Owen M.J. Meta-analysis of association between the 5-HT2a receptor T102C polymorphism and schizophrenia. EMASS Collaborative Group. European Multicentre Association Study of Schizophrenia. Lancet 349 (1997) 1221
52. Yates M., Leake A., Candy J.M., Fairbairn A.F., McKeith I.G., and Ferrier I.N. 5HT2 receptor changes in major depression. Biol Psychiatry 27 (1990) 489-496
53. Zhu Q.S., Chen K., and Shih J.C. Characterization of the human 5-HT2A receptor gene promoter. J Neurosci 15 (1995) 4885-4895