Lack of evidence for association of the serotonin transporter gene SLC6A4 with autism.
BACKGROUND
The serotonin transporter (5-HTT) has long been considered likely to play a role in autism. Hyperserotonemia has been consistently found in a proportion of autistic patients, and the use of selective serotonin reuptake inhibitors (SSRIs) can have a positive effect in treating some symptoms of autism. Specific variants of the 5-HTT gene, SLC6A4, especially the insertion-deletion 5-HTTLPR promoter locus, have been found to modulate its expression and transporter function.


METHODS
We examined the transmission of the short or long allele of 5-HTTLPR locus to affected individuals, using a large cohort of 352 families. In addition, we screened five single nucleotide polymorphisms (SNPs) in the 5' region of SLC6A4 previously reported to be positively associated with autism, as well as 4 additional SNPs also in the 5' region.


RESULTS
No association of the 5-HTTLPR locus with autism was found. Furthermore, no evidence for association of any of the nine SNPs covering the SLC6A4 gene, or any of their haplotypes, was observed in our study. Using obsessive-compulsive behaviors (OCB), severe OCBs or rigid-compulsive subsets of our cohort gave the same negative results.


CONCLUSIONS
SLC6A4 variants do not appear to be significantly involved in the liability to autism.
Ramoz
Nicolas
N
Laboratory of Molecular Neuropsychiatry, Department of Psychiatry, Seaver Autism Research Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
Reichert
Jennifer G
JG
Corwin
Thomas E
TE
Smith
Christopher J
CJ
Silverman
Jeremy M
JM
Hollander
Eric
E
Buxbaum
Joseph D
JD
D001321:Autistic Disorder / Q000235:genetics*; D015331:Cohort Studies; D003192:Compulsive Behavior / Q000235:genetics; D004247:DNA / Q000235:genetics; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D009771:Obsessive-Compulsive Disorder / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
D005819:Genetic Markers; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D004247:DNA