Summary.
Serotonin transporter gene (SLC6A4) is one of the most promising candidate genes for psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BP). Two functional polymorphisms, 5HTTLPR and 5HTTVNTR, have been a focus for genetic association analyses; however, no conclusive results have been obtained. We conducted, 1) a mutation search of SLC6A4, 2) LD mapping to select ‘tagging’ markers (10 SNPs and 5HTTVNTR, while 5HTTLPR was treated as an independent marker because of its allelic form), and 3) association analysis of these ‘tagging’ markers and independent markers (5HTTLPR and Asn605Lys) with SCZ and BP in Japanese patients. In this mutation search, a nonsynonymous SNP, Asn605Lys, was detected. No associations of ‘tagging’ markers and independent markers with such conditions were found. These results indicate that SLC6A4 might not play a major role in SCZ and BP in Japanese patients, a finding that agrees with both the common disease-common variant hypothesis and common disease-rare variant hypothesis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
M Anguelova C Benkelfat G Turecki (2003) ArticleTitleA systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter. Affective disorders Mol Psychiatry 8 574–591 Occurrence Handle12851635 Occurrence Handle1:CAS:528:DC%2BD3sXltFylsrY%3D Occurrence Handle10.1038/sj.mp.4001328
JC Barrett B Fry J Maller MJ Daly (2005) ArticleTitleHaploview: analysis and visualization of LD and haplotype maps Bioinformatics 21 263–265 Occurrence Handle15297300 Occurrence Handle1:CAS:528:DC%2BD2MXkt1WitQ%3D%3D Occurrence Handle10.1093/bioinformatics/bth457
S Battersby AD Ogilvie DH Blackwood S Shen MM Muqit WJ Muir P Teague GM Goodwin AJ Harmar (1999) ArticleTitlePresence 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 Occurrence Handle10098839 Occurrence Handle1:CAS:528:DyaK1MXitFCksrg%3D Occurrence Handle10.1046/j.1471-4159.1999.721384.x
A Chakravarti (1999) ArticleTitlePopulation genetics – making sense out of sequence Nat Genet 21 56–60 Occurrence Handle9915503 Occurrence Handle1:CAS:528:DyaK1MXltlWhuw%3D%3D Occurrence Handle10.1038/4482
JS Collins CE Schwartz (2002) ArticleTitleDetecting polymorphisms and mutations in candidate genes Am J Hum Genet 71 1251–1252 Occurrence Handle12452182 Occurrence Handle1:CAS:528:DC%2BD38XovFOns78%3D Occurrence Handle10.1086/344344
F Dudbridge (2003) ArticleTitlePedigree disequilibrium tests for multilocus haplotypes Genet Epidemiol 25 115–121 Occurrence Handle12916020 Occurrence Handle10.1002/gepi.10252
D Hranilovic J Stefulj S Schwab M Borrmann-Hassenbach M Albus B Jernej D Wildenauer (2004) ArticleTitleSerotonin transporter promoter and intron 2 polymorphisms: relationship between allelic variants and gene expression Biol Psychiatry 55 1090–1094 Occurrence Handle15158428 Occurrence Handle1:CAS:528:DC%2BD2cXktF2murg%3D Occurrence Handle10.1016/j.biopsych.2004.01.029
X Ke LR Cardon (2003) ArticleTitleEfficient selective screening of haplotype tag SNPs Bioinformatics 19 287–288 Occurrence Handle12538253 Occurrence Handle1:CAS:528:DC%2BD3sXitlCnsbs%3D Occurrence Handle10.1093/bioinformatics/19.2.287
JA Lasky-Su SV Faraone SJ Glatt MT Tsuang (2005) ArticleTitleMeta-analysis of the association between two polymorphisms in the serotonin transporter gene and affective disorders Am J Med Genet B Neuropsychiatr Genet 133 110–115 Occurrence Handle15578606
KP Lesch D Bengel A Heils SZ Sabol BD Greenberg S Petri J Benjamin CR Muller DH Hamer DL Murphy (1996) ArticleTitleAssociation of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region Science 274 1527–1531 Occurrence Handle8929413 Occurrence Handle1:CAS:528:DyaK28Xnt1ansL8%3D Occurrence Handle10.1126/science.274.5292.1527
M Nakamura S Ueno A Sano H Tanabe (2000) ArticleTitleThe human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants Mol Psychiatry 5 32–38 Occurrence Handle10673766 Occurrence Handle1:CAS:528:DC%2BD3cXlslarsL4%3D Occurrence Handle10.1038/sj.mp.4000698
AD Ogilvie S Battersby VJ Bubb G Fink AJ Harmar GM Goodwim CA Smith (1996) ArticleTitlePolymorphism in serotonin transporter gene associated with susceptibility to major depression Lancet 347 731–733 Occurrence Handle8602004 Occurrence Handle1:CAS:528:DyaK28Xitl2hurw%3D Occurrence Handle10.1016/S0140-6736(96)90079-3
J Ohashi S Yamamoto N Tsuchiya Y Hatta T Komata M Matsushita K Tokunaga (2001) ArticleTitleComparison of statistical power between 2 * 2 allele frequency and allele positivity tables in case-control studies of complex disease genes Ann Hum Genet 65 197–206 Occurrence Handle11434330 Occurrence Handle1:STN:280:DC%2BD3MznslaisQ%3D%3D Occurrence Handle10.1017/S000348000100851X
Ozaki N, Goldman D, Kaye WH, Plotnicov K, Greenberg BD, Lappalainen J, Rudnick G, Murphy DL (2003) Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype. Mol Psychiatry 8: 895, 933–996
JK Pritchard NJ Cox (2002) ArticleTitleThe allelic architecture of human disease genes: common disease-common variant … or not? Hum Mol Genet 11 2417–2423 Occurrence Handle12351577 Occurrence Handle1:CAS:528:DC%2BD38XnvVenu7k%3D Occurrence Handle10.1093/hmg/11.20.2417
A Serretti R Lilli C Lorenzi E Lattuada C Cusin E Smeraldi (2002) ArticleTitleSerotonin transporter gene (5-HTTLPR) and major psychoses Mol Psychiatry 7 95–99 Occurrence Handle11803453 Occurrence Handle1:CAS:528:DC%2BD38XhsVGlsrw%3D Occurrence Handle10.1038/sj.mp.4001936
HS Sun HC Wang TJ Lai TJ Wang CM Li (2004) ArticleTitleSequence variants and haplotype analysis of serotonin transporter gene and association with bipolar affective disorder in Taiwan Pharmacogenetics 14 173–179 Occurrence Handle15167705 Occurrence Handle1:CAS:528:DC%2BD2cXjt1KjsrY%3D Occurrence Handle10.1097/00008571-200403000-00005
T Suzuki N Iwata Y Kitamura T Kitajima Y Yamanouchi M Ikeda T Nishiyama N Kamatani N Ozaki (2003) ArticleTitleAssociation of a haplotype in the serotonin 5-HT4 receptor gene (HTR4) with Japanese schizophrenia Am J Med Genet 121B 7–13 Occurrence Handle10.1002/ajmg.b.20060
SJ Tsai WC Ouyang CJ Hong (2002) ArticleTitleAssociation for serotonin transporter gene variable number tandem repeat polymorphism and schizophrenic disorders Neuropsychobiology 45 131–133 Occurrence Handle11979062 Occurrence Handle1:CAS:528:DC%2BD38XjtlSjtrc%3D Occurrence Handle10.1159/000054952
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ikeda, M., Iwata, N., Suzuki, T. et al. 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 (2006). https://doi.org/10.1007/s00702-005-0349-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-005-0349-6