Serotonin transporter promoter and intron 2 polymorphisms: Relationship between allelic variants and gene expression

被引:189
作者
Hranilovic, D
Stefulj, J
Schwab, S
Borrmann-Hassenbach, M
Albus, M
Jernej, B
Wildenauer, D
机构
[1] Rudjer Boskovic Inst, Dept Mol Genet, Lab Neurochem & Mol Neurobiol, HR-10000 Zagreb, Croatia
[2] Dist Hosp Haar, Haar, Germany
[3] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany
关键词
5-hydroxytryptamine; mRNA; real-time PCR; 5-HTTLPR; VNTR-2; lymphoblasts; schizophrenia;
D O I
10.1016/j.biopsych.2004.01.029
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: Two polymorphic regions of serotonin transporter (5-HTT) gene: a 44 base pair (hp) insertion/deletion in the promoter region (5-HTTLPR) and a 17 bp variable number of tandem repeats in second intron (VNTR-2), seem to modulate the gene's transcription in allele-dependent manner. Methods: We have earlier demonstrated association with 5-HTT gene in families multiply affected by schizophrenia. Here, we investigated separate and combined effects of VNTR-2 and 5-HTTLPR on the rate of peripheral 5-HTT transcription in a sample of offspring from those families. Relative 5-HTT mRNA levels were determined in 53 permanent lymphoblast cell lines by semiquantitative real-time polymerase chain reaction using beta-actin as reference. Results: Since the low-expressing alleles (short [S], 10) appeared to act dominantly, genotypes were grouped as "high-expressing" (long [L]/L, 12/12) versus "low-expressing" (S, 10). At both loci, nonsignificant differences in 5-HTT mRNA levels (similar to30%) were observed between "high"- and "low-expressing" genotypes. In order to search for the potential combined effect of 5-HTTLPR and VNTR-2, levels of 5-HTT mRNA were compared among three groups of samples having "low-expressing" genotype at none, one, or both loci. Increase in number of ''low-expressing" genotypes significantly reduced relative 5-HTT gene expression (p < .02). Conclusions: Our results indicate weak individual influence, but possible combined effect, of 5-HTTLPR and VNTR-2 polymorphisms on 5-HTT gene expression.
引用
收藏
页码:1090 / 1094
页数:5
相关论文
共 49 条
  • [1] Presence of multiple functional polyadenylation signals and a single nucleotide polymorphism in the 3′ untranslated region of the human serotonin transporter gene
    Battersby, S
    Ogilvie, AD
    Blackwood, DHR
    Shen, SB
    Muqit, MMK
    Muir, WJ
    Teague, P
    Goodwin, GM
    Harmar, AJ
    [J]. JOURNAL OF NEUROCHEMISTRY, 1999, 72 (04) : 1384 - 1388
  • [2] Serotonin transporter gene polymorphism and schizophrenia: An association study
    BonnetBrilhault, F
    Laurent, C
    Thibaut, F
    Campion, D
    Chavand, O
    Samolyk, D
    Martinez, M
    Petit, M
    Mallet, J
    [J]. BIOLOGICAL PSYCHIATRY, 1997, 42 (07) : 634 - 636
  • [3] Bradley CC, 1997, J NEUROCHEM, V69, P1356
  • [4] Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays
    Bustin, SA
    [J]. JOURNAL OF MOLECULAR ENDOCRINOLOGY, 2000, 25 (02) : 169 - 193
  • [5] Functionally gene-linked polymorphic regions and genetically controlled neurotransmitters metabolism
    Catalano, M
    [J]. EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2001, 11 (06) : 431 - 439
  • [6] de Oliveira JRM, 1998, AM J MED GENET, V81, P225, DOI 10.1002/(SICI)1096-8628(19980508)81:3<225::AID-AJMG4>3.0.CO
  • [7] 2-V
  • [8] An intronic polymorphic domain often associated with susceptibility to affective disorders has allele dependent differential enhancer activity in embryonic stem cells
    Fiskerstrand, CE
    Lovejoy, EA
    Quinn, JP
    [J]. FEBS LETTERS, 1999, 458 (02) : 171 - 174
  • [9] Modified structure of the human serotonin transporter promoter
    Flattem, NL
    Blakely, RD
    [J]. MOLECULAR PSYCHIATRY, 2000, 5 (01) : 110 - 115
  • [10] Gelernter J, 1999, AM J MED GENET, V88, P61, DOI 10.1002/(SICI)1096-8628(19990205)88:1<61::AID-AJMG11>3.0.CO