Elsevier

Biological Psychiatry

Volume 60, Issue 2, 15 July 2006, Pages 186-191
Biological Psychiatry

Original article
Lack of Evidence for Association of the Serotonin Transporter Gene SLC6A4 with Autism

https://doi.org/10.1016/j.biopsych.2006.01.009Get rights and content

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.

Section snippets

Subjects and Subsets of Autism Families

A total of 352 families were either recruited by the Seaver Autism Research Center (SARC)/Greater New York Autism Research Center for Excellence/STAART Center at Mount Sinai (n = 57), corecruited by the SARC and the Autism Genetic Resource Exchange (AGRE) (n = 130), or obtained from AGRE (n = 165) (Geschwind et al 2001). All parents provided written informed consent. The Autism Diagnostic Interview—Revised (ADI-R) was used for the clinical assessment of affected subjects. Individuals with

No Linkage Between Markers of SLC6A4 and Autism

The 5-HTTLPR locus and 9 SNPs that cover the 5′ half of SLC6A4 gene, including five SNPs previously shown to be positive, were genotyped in 352 families (Figure 1). Accuracy of genotyping has been estimated to > 99.99% by checking 120 individuals in duplicates or triplicates and 27 pairs of monozygote twins. Markers were confirmed to be in Hardy–Weinberg equilibrium and their allelic frequencies and heterozygosity rates were similar to those reported in the NCBI SNP database and in

Discussion

Autism appears to be one of the most highly genetic of the neuropsychiatric disorders. We examined the 5-HT transporter, SLC6A4, in a large cohort of autism families and according to specific endophenotype subsets.

We analyzed the promoter 5-HTTLPR insertion–deletion polymorphisms and nine SNPs within the SLC6A4 gene to evaluate whether these polymorphisms were associated with autism or with certain symptom domains. No significant overtransmission for the S or L allele of 5-HTTLPR was found, nor

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