Major psychiatric disorders and the serotonin transporter gene (SLC6A4): family-based association studies.
The serotonin transporter (5-HTT) is a suitable candidate gene to test for involvement in the pathogenesis of major psychiatric disorders. We used the method of family-based controls to test for association between disease and a variable number tandem repeat (VNTR) in intron 2 of the gene, which has received support for involvement in the pathogenesis of several psychiatric disorders. We analysed 413 proband-parent trios of Bulgarian origin: 266 had a schizophrenic proband, 103 had a bipolar proband and 44 had a schizoaffective proband. The results were analysed using the extended transmission disequilibrium test. Possible effects of different alleles on certain clinical variables were examined by correlation analysis. Three alleles were detected: STin2.9, STin2.10 and STin2.12. None of the three diagnostic samples showed preferential transmission of alleles that reached conventional levels of statistical significance. We could not confirm previous results that STin2.12 allele increases susceptibility to bipolar disorder type I. The rare STin2.9 showed a non-significant trend for preferential transmission in the sample as a whole: 18 transmitted versus 11 non-transmitted (P = 0.2). The VNTR polymorphism in the 5-HTT gene does not appear to be a major risk factor for increasing susceptibility to major psychiatric disorders.
Dimitrova
Albena
A
Department of Medical Genetics, Medical University Sofia, University Hospital Maichin dom, Sofia, Bulgaria.
Georgieva
Lyudmila
L
Nikolov
Ivan
I
Poriazova
Nadejda
N
Krastev
Stefan
S
Toncheva
Draga
D
Owen
Michael J
MJ
Kirov
George
G
D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics; D002031:Bulgaria / Q000208:ethnology; D002352:Carrier Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D007438:Introns; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D018598:Minisatellite Repeats; D009419:Nerve Tissue Proteins; D011618:Psychotic Disorders / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins