Detailed analysis of the serotonin transporter gene (SLC6A4) shows no association with bipolar disorder in the Northern Swedish population.
Through active reuptake of serotonin into presynaptic neurons, the serotonin transporter (5-HTT) plays an important role in regulating serotonin concentrations in the brain, and it is the site of binding for tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs). Therefore it has been hypothesized that this transporter is involved in the etiology of bipolar (BP) disorder. Inconsistent association study results for the SLC6A4 gene encoding 5-HTT reported in literature emphasize the need for more systematic and detailed analyses of this candidate gene. We performed an extensive analysis of SLC6A4 on DNA of 254 BPI patients and 364 control individuals from a Northern Swedish isolated population. This analysis consisted of a HapMap LD-based association study including three widely investigated polymorphisms (5-HTTVNTR, 5-HTTLPR, and rs3813034), a copy-number variation (CNV) analysis and a mutation analysis of the complete coding sequence and the 3'-UTR of SLC6A4. No single marker showed statistically significant association with BPI, nor did any of the haplotypes. In the mutation analysis 13 novel variants were detected, including 2 amino acid substitutions M389V and I587L, but these are probably not implicated in risk for BP. No deletions or duplications were detected in the CNV analysis. We conclude that variation in the SLC6A4 gene or its regulatory regions does not contribute to the susceptibility for BP disorder in the Northern Swedish population.
Alaerts
Maaike
M
Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
Ceulemans
Shana
S
Forero
Diego
D
Moens
Lotte N
LN
De Zutter
Sonia
S
Heyrman
Lien
L
Lenaerts
An-Sofie
AS
Norrback
Karl-Fredrik
KF
Goossens
Dirk
D
De Rijk
Peter
P
Nilsson
Lars-Göran
LG
Adolfsson
Rolf
R
Del-Favero
Jurgen
J
D000483:Alleles; D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins