The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants.
The serotonin transporter (5-HTT) gene is a promising candidate for introducing the heritability of interindividual variation in personality and the genetic susceptibility for various psychiatric diseases. Transcription of the gene is modulated by a common polymorphism in its upstream regulatory region (5-HTT gene-linked polymorphic region: 5-HTTLPR). The 5-HTTLPR consists of variation of the repetitive sequence containing GC-rich, 20-23-bp-long repeat elements. A deletion/insertion in the 5-HTTLPR was first reported to create a short (S) allele and a long (L) allele (14- and 16-repeats, respectively). Three other kinds of alleles (18-, 19- and 20-repeats) in addition to the S and L alleles in 5-HTTLPR have been reported. In the present study, we examined the 5-HTTLPR polymorphism in detail and identified ten novel sequence variants, concluding that the alleles reported as S and L are divided into four and six kinds of allelic variant, respectively. Subsequently, we developed a method for genotyping. The total number of alleles (14-A, 14-B, 14-C, 14-D, 15, 16-A, 16-B, 16-C, 16-D, 16-E, 16-F, 19, 20 and 22) in the 5-HTTLPR was 14 in our populations (Japanese: n = 131; Caucasian: n = 74) in the present study. In addition, a significant ethnic difference between Japanese and Caucasian populations was observed for distributions of alleles and genotypes (P < 0.0001 and P < 0.0001, respectively). Our results suggest that the analyses of the 5-HTTLPR should be revised by genotyping with a more complete subdivision of alleles. Molecular Psychiatry (2000) 5, 32-38.
Nakamura
M
M
The Department of Neuropsychiatry, Ehime University School of Medicine, Shitsukawa, Shigenobu, Onsen-gun, Ehime 791-0295, Japan.
Ueno
S
S
Sano
A
A
Tanabe
H
H
D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D005838:Genotype; D020180:Heteroduplex Analysis; D006801:Humans; D007564:Japan; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012150:Polymorphism, Restriction Fragment Length; D012091:Repetitive Sequences, Nucleic Acid; D050486:Serotonin Plasma Membrane Transport Proteins; D044465:White People / Q000235:genetics*
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins