Detailed analysis of the serotonin transporter gene (SLC6A4) shows no association with bipolar disorder in the Northern Swedish population

American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

Volumn 150, Issue 4, 2009, Pages 585-592

  Alaerts, Maaike ^a,b   Ceulemans, Shana ^a,b   Forero, Diego ^a,b   Moens, Lotte N ^a,b   De Zutter, Sonia ^a,b   Heyrman, Lien ^a,b   Lenaerts, An Sofie ^a,b   Norrback, Karl Fredrik ^c,d   Goossens, Dirk ^a,b   De Rijk, Peter ^a,b   Nilsson, Lars Göran ^e   Adolfsson, Rolf ^c,d   Del Favero, Jurgen ^a,b  

^a DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^b UNIVERSITY OF ANTWERP   (Belgium)

^c UMEÅ UNIVERSITY   (Sweden)

^d Sunderby County Hospital   (Sweden)

^e STOCKHOLM UNIVERSITY   (Sweden)

Author keywords

Bipolar disorder; Copy number variation; Linkage disequilibrium; Mutation analysis; Serotonin transporter; SLC6A4

Indexed keywords

SEROTONIN TRANSPORTER;

AMINO ACID SUBSTITUTION; ARTICLE; BIPOLAR DISORDER; CONTROLLED STUDY; DNA DETERMINATION; GENE; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HAPLOTYPE; HUMAN; LINKAGE ANALYSIS; MAJOR CLINICAL STUDY; MUTATIONAL ANALYSIS; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; SLC6A4 GENE; SWEDEN;

ALLELES; BIPOLAR DISORDER; EXONS; GENE FREQUENCY; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HAPLOTYPES; HUMANS; INTRONS; MUTATION; POLYMORPHISM, SINGLE NUCLEOTIDE; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SWEDEN;

EID: 66649107296     PISSN: 15524841     EISSN: 1552485X     Source Type: Journal    
DOI: 10.1002/ajmg.b.30853     Document Type: Article

References (45)

1. American Psychiatry Association. 1994. Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Washington, DC: American Psychiatric Press.
2. Anguelova M, Benkelfat C, Turecki G. 2003. A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: I. Affective disorders. Mol Psychiatry 8:574-591.
3. Bartel DP. 2004. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 116:281-297. (Pubitemid 38167318)
4. Battersby S, Ogilvie AD, Blackwood DH, Shen S, Muqit MM, Muir WJ, Teague P, Goodwin GM, Harmar AJ. 1999. Presence of multiple functional polyadenylation signals and a single nucleotide polymorphism in the 3′ untranslated region of the human serotonin transporter gene. J Neurochem 72:1384-1388. (Pubitemid 29140806)
5. Cho HJ, Meira-Lima I, Cordeiro Q, Michelon L, Sham P, Vallada H, Collier DA. 2005. Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: A systematic review and meta-analysis. Mol Psychiatry 10:771-781. (Pubitemid 41129050)
6. Collier DA, Arranz MJ, Sham P, Battersby S, Vallada H, Gill P, Aitchison KJ, Sodhi M, Li T, Roberts GW, Smith B, Morton J, Murray RM, Smith D, Kirov G. 1996. The serotonin transporter is a potential susceptibility factor for bipolar affective disorder. Neuroreport 7: 1675-1679. (Pubitemid 26332347)
7. Di Bella D, Catalano M, Balling U, Smeraldi E, Lesch KP. 1996. Systematic screening for mutations in the coding region of the human serotonin transporter (5-HTT) gene using PCR and DGGE. Am J Med Genet 67:541-545. (Pubitemid 26411938)
8. Faraone SV, Lasky-Su J, Glatt SJ, Van Eerdewegh P, Tsuang MT. 2006. Early onset bipolar disorder: Possible linkage to chromosome 9q34. Bipolar Disord 8:144-151. (Pubitemid 44026766)
9. Feuk L, Carson AR, Scherer SW. 2006. Structural variation in the human genome. Nat Rev Genet 7:85-97. (Pubitemid 43128895)
10. Fiskerstrand CE, Lovejoy EA, Quinn JP. 1999. An intronic polymorphic domain often associated with susceptibility to affective disorders has allele dependent differential enhancer activity in embryonic stem cells. FEBS Lett 458:171-174. (Pubitemid 29428177)
11. Furlong RA, Ho L, Walsh C, Rubinsztein JS, Jain S, Paykel ES, Easton DF, Rubinsztein DC. 1998. Analysis and meta-analysis of two serotonin transporter gene polymorphisms in bipolar and unipolar affective disorders. Am J Med Genet 81:58-63. (Pubitemid 28114852)
12. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D. 2002. The structure of haplotype blocks in the human genome. Science 296:2225-2229. (Pubitemid 34680308)
13. Ghaemi SN, Hsu DJ, Soldani F, Goodwin FK. 2003. Antidepressants in bipolar disorder: The case for caution. Bipolar Disord 5:421-433. (Pubitemid 38072244)
14. Glatt CE, DeYoung JA, Delgado S, Service SK, Giacomini KM, Edwards RH, Risch N, Freimer NB. 2001. Screening a large reference sample to identify very low frequency sequence variants: Comparisons between two genes. Nat Genet 27:435-438. (Pubitemid 32268427)
15. Greenberg BD, Tolliver TJ, Huang SJ, Li Q, Bengel D, Murphy DL. 1999. Genetic variation in the serotonin transporter promoter region affects serotonin uptake in human blood platelets. Am J Med Genet 88:83-87. (Pubitemid 29075327)
16. Gutierrez B, Arranz MJ, Collier DA, Valles V, Guillamat R, Bertranpetit J, Murray RM, Fanas L. 1998. Serotonin transporter gene and risk for bipolar affective disorder: An association study in Spanish population. Biol Psychiatry 43:843-847. (Pubitemid 28288384)
17. Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D, Lesch KP. 1996. Allelic variation of human serotonin transporter gene expression. J Neurochem 66:2621-2624. (Pubitemid 26159101)
18. Hoehe MR, Wendel B, Grunewald I, Chiaroni P, Levy N, Morris-Rosendahl D, Macher JP, Sander T, Crocq MA. 1998. Serotonin transporter (5-HTT) gene polymorphisms are not associated with susceptibility to mood disorders. Am J Med Genet 81:1-3.
19. Hranilovic D, Stefulj J, Schwab S, Borrmann-Hassenbach M, Albus M, Jernej B, Wildenauer D. 2004. Serotonin transporter promoter and intron 2 polymorphisms: Relationship between allelic variants and gene expression. Biol Psychiatry 55:1090-1094. (Pubitemid 38680561)
20. Hu XZ, Lipsky RH, Zhu G, Akhtar LA, Taubman J, Greenberg BD, Xu K, Arnold PD, Richter MA, Kennedy JL, Murphy DL, Goldman D. 2006. Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. Am J Hum Genet 78:815-826.
21. Ikeda M, Iwata N, Suzuki T, Kitajima T, Yamanouchi Y, Kinoshita Y, Ozaki N. 2005. No association of serotonin transporter gene (SLC6A4) with schizophrenia and bipolar disorder in Japanese patients: Association analysis based on linkage disequilibrium. J Neural Transm 113:899-905.
22. Kahn DA, Sachs GS, Printz DJ, Carpenter D, Docherty JP, Ross R. 2000. Medication treatment of bipolar disorder 2000: A summary of the expert consensus guidelines. J Psychiatr Pract 6:197-211.
23. Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT. 2008. Initial severity and antidepressant benefits: A meta-analysis of data submitted to the Food and Drug Administration. PLoS Med 5:e45.
24. Lasky-Su JA, Faraone SV, Glatt SJ, Tsuang MT. 2005. Meta-analysis of the association between two polymorphisms in the serotonin transporter gene and affective disorders. Am J Med Genet Part B 133B: 110-115. (Pubitemid 40175627)
25. Lesch KP, Balling U, Gross J, Strauss K, Wolozin BL, Murphy DL, Riederer P. 1994. Organization of the human serotonin transporter gene. J Neural Transm Gen Sect 95:157-162. (Pubitemid 2051960)
26. Lesch KP, Gross J, Franzek E, Wolozin BL, Riederer P, Murphy DL. 1995. Primary structure of the serotonin transporter in unipolar depression and bipolar disorder. Biol Psychiatry 37:215-223.
27. Lesch K, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Müller CR, Hamer DH, Murphy DL. 1996. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274:1527-1531. (Pubitemid 26403928)
28. Lin PI, McInnis MG, Potash JB, Willour V, MacKinnon DF, DePaulo JR, Zandi PP. 2006. Clinical correlates and familial aggregation of age at onset in bipolar disorder. Am J Psychiatry 163:240-246.
29. Lotrich FE, Pollock BG. 2004. Meta-analysis of serotonin transporter polymorphisms and affective disorders. Psychiatr Genet 14:121-129. (Pubitemid 39281818)
30. MacKenzie A, Quinn J. 1999. A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo. Proc Natl Acad Sci USA 96:15251-15255. (Pubitemid 30019798)
31. Mansour HA, Talkowski ME, Wood J, Pless L, Bamne M, Chowdari KV, Allen M, Bowden CL, Calabrese J, El Mallakh RS, Fagiolini A, Faraone SV, Fossey MD, Friedman ES, Gyulai L, Hauser P, Ketter TA, Loftis JM, Marangell LB, Miklowitz DJ, Nierenberg AA, Patel J, Sachs GS, Sklar P, Smoller JW, Thase ME, Frank E, Kupfer DJ, Nimgaonkar VL. 2005. Serotonin gene polymorphisms and bipolar I disorder: Focus on the serotonin transporter. Ann Med 37:590-602. (Pubitemid 41780147)
32. Martin J, Cleak J, Willis-Owen SA, Flint J, Shifman S. 2007. Mapping regulatory variants for the serotonin transporter gene based on allelic expression imbalance. Mol Psychiatry 12:421-422. (Pubitemid 46652459)
33. Mendlewicz J, Massat I, Souery D, Del Favero J, Oruc L, Nothen MM, Blackwood D, Muir W, Battersby S, Lerer B, Segman RH, Kaneva R, Serretti A, Lilli R, Lorenzi C, Jakovljevic M, Ivezic S, Rietschel M, Milanova V, Van Broeckhoven C. 2004. Serotonin transporter 5HTTLPR polymorphism and affective disorders: No evidence of association in a large European multicenter study. Eur J Hum Genet 12:377-382.
34. Mundo E, Walker M, Tims H, Macciardi F, Kennedy JL. 2000. Lack of linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and bipolar disorder. Am J Med Genet 96:379-383. (Pubitemid 30662503)
35. Mynett-Johnson L, Kealey C, Claffey E, Curtis D, Bouchier-Hayes L, Powell C, McKeon P. 2000. Multimarker haplotypes within the serotonin transporter gene suggest evidence of an association with bipolar disorder. Am J Med Genet 96:845-849.
36. Nadeau JH, Lee C. 2006. Genetics: Copies count. Nature 439:798-799. (Pubitemid 43255688)
37. Philibert RA, Sandhu H, Hollenbeck N, Gunter T, Adams W, Madan A. 2007. The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies. Am J Med Genet B Neuropsychiatr Genet 147:543-549.
38. Rees M, Norton N, Jones I, McCandless F, Scourfield J, Holmans P, Moorhead S, Feldman E, Sadler S, Cole T, Redman K, Farmer A, McGuffin P, Owen MJ, Craddock N. 1997. Association studies of bipolar disorder at the human serotonin transporter gene (hSERT; 5HTT). Mol Psychiatry 2:398-402. (Pubitemid 127702160)
39. Rotondo A, Mazzanti C, Dell'Osso L, Rucci P, Sullivan P, Bouanani S, Gonnelli C, Goldman D, Cassano GB. 2002. Catechol o-methyltransferase, serotonin transporter, and tryptophan hydroxylase gene polymorphisms in bipolar disorder patients with and without comorbid panic disorder. Am J Psychiatry 159:23-29. (Pubitemid 41070722)
40. Sakai K, Nakamura M, Ueno S, Sano A, Sakai N, Shirai Y, Saito N. 2002. The silencer activity of the novel human serotonin transporter linked polymorphic regions. Neurosci Lett 327:13-16. (Pubitemid 34722432)
41. Suls A, Claeys KG, Goossens D, Harding B, Van Luijk R, Scheers S, Deprez L, Audenaert D, Van Dyck T, Beeckmans S, Smouts I, Ceulemans B, Lagae L, Buyse G, Barisic N, Misson JP, Wauters J, Del Favero J, De Jonghe P, Claes LR. 2006. Microdeletions involving the SCN1A gene may be common in SCN1A-mutation-negative SMEI patients. Hum Mutat 27:914-920. (Pubitemid 44336941)
42. Sun HS, Wang HC, Lai TJ, Wang TJ, Li CM. 2004. Sequence variants and haplotype analysis of serotonin transporter gene and association with bipolar affective disorder in Taiwan. Pharmacogenetics 14:173-179. (Pubitemid 38373111)
43. Vincent JB, Masellis M, Lawrence J, Choi V, Gurling HM, Parikh SV, Kennedy JL. 1999. Genetic association analysis of serotonin system genes in bipolar affective disorder. Am J Psychiatry 156:136-138. (Pubitemid 29034893)
44. Weckx S, Del Favero J, Rademakers R, Claes L, Cruts M, De Jonghe P, Van Broeckhoven C, De Rijk P. 2005. novoSNP, a novel computational tool for sequence variation discovery. Genome Res 15:436-442. (Pubitemid 40467785)
45. Yamashita A, Singh SK, Kawate T, Jin Y, Gouaux E. 2005. Crystal structure of a bacterial homologue of Na+/Cl- dependent neurotransmitter transporters. Nature 437:215-223. (Pubitemid 41294479)