title: Allelic association analysis of the functional insertion/deletion polymorphism in the promoter region of the serotonin transporter gene in bipolar affective disorder.
abstract: The human serotonin transporter gene (5-HTT) is a candidate for the pathogenesis of mood disorders, including bipolar disorder (BPD). The 5-HTT gene has a 44-bp insertion/deletion polymorphism within the promoter region (5-HTTLPR) with 2 allelic forms, the long (l) and the short (s) variants, which affect transcriptional rates of the 5-HTT gene. Association between the low-activity s variant and BPD has been suggested but remains controversial, as replication has not been consistent. In the present study, we examined the frequency of this polymorphism in a group of 266 Brazilian BPD patients and 306 control subjects. Genotyping for the 5-HTTLPR was performed using PCR. The allele frequencies were found to differ between BPD patients and controls (p=0.03), with a higher frequency of the l allele in the patients compared with the controls (60.5% vs 54.4%). The distribution of genotypes also differed significantly between cases and controls (chi2=10.4, 2 df, p=0.005), with higher frequency of heterozygous l/s genotype in the BPD patient group (52.6% vs 44%). Because prior evidence from gene expression studies indicated that l/s and s/s genotypes are not distinguishable biochemically, we compared the distribution of the l/l genotype and the combined group l/s plus s/s between case and controls, but there was no significant difference (chi2=0.22). Likewise, a logistic regression model considering a dominant role for the s variant was not significant (OR=0.92, 95% CI 0.64-1.32). Our results suggest that the low-activity s variant does not influence susceptibility to BPD in our population.
authors.affiliation: PROGENE (LIM 23), Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil, and Section of General Hospital Psychiatry, Institute of Psychiatry, King's College London, UK.
authors.forename: Ivanor
authors.initials: I
authors.lastname: Meira-Lima
authors.forename: Leandro
authors.initials: L
authors.lastname: Michelon
authors.forename: Quirino
authors.initials: Q
authors.lastname: Cordeiro
authors.forename: Hyong Jin
authors.initials: HJ
authors.lastname: Cho
authors.forename: Homero
authors.initials: H
authors.lastname: Vallada
mesh_terms: D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics* / Q000503:physiopathology*; D001938:Brazil; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins