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Thursday, May 15, 2008
Champagne Terrace/Bordeaux (Novotel London West)
11:30 AM
Background: A role for the serotoninergic system in autism has long been suggested based on its implication in behavioural processes such as social interactions and the frequent observation of elevated levels of blood platelet serotonin in autistic patients.
Objectives: We tested for an association between the SLC6A4 gene encoding the serotonin transporter (5-HTT) and autism or non syndromic mental deficiency (MD). We next analyzed the expression levels and methylation status of SLC6A4 in lymphoblastoïde cell lines from autistic patients.
Methods: We genotyped four functional polymorphisms (rs25531 and 5-HTTLPR in the promoter, VNTR in intron 2, rs3813034 in 3’UTR) in the SLC6A4 gene (17q12) in a population with autism (n = 103), a population with non syndromic MD (n = 100) and a control population (n = 164).
Results: We did not observe significant differences in the distributions of alleles and genotypes between patients with MD and controls. However, we found significant differences in allele frequencies for the 5-HTTLPR marker (X2=13.38, p=0.00025; Odds ratio 1.93, CI 95%:1.35-2.75) and haplotype frequencies (X2=13.93, p=0.003) between autistic patients and controls. The autistic patients showed higher frequencies of the Short (S) allele of 5-HTTLPR and the A / S haplotypes (rs25531 / 5-HTTLPR). We are currently analysing the expression level and the methylation status of the SLC6A4 gene in lymphoblastoïde cell lines from autistic patients carrying different genotypes for 5-HTTLPR (Long/Long, Long/Short, Short/Short). These experiments are performed on lymphoblastoïde cells cultured with or without brain neurotrophic factor (BDNF), molecule acting on the serotoninergic system.
Objectives: We tested for an association between the SLC6A4 gene encoding the serotonin transporter (5-HTT) and autism or non syndromic mental deficiency (MD). We next analyzed the expression levels and methylation status of SLC6A4 in lymphoblastoïde cell lines from autistic patients.
Methods: We genotyped four functional polymorphisms (rs25531 and 5-HTTLPR in the promoter, VNTR in intron 2, rs3813034 in 3’UTR) in the SLC6A4 gene (17q12) in a population with autism (n = 103), a population with non syndromic MD (n = 100) and a control population (n = 164).
Results: We did not observe significant differences in the distributions of alleles and genotypes between patients with MD and controls. However, we found significant differences in allele frequencies for the 5-HTTLPR marker (X2=13.38, p=0.00025; Odds ratio 1.93, CI 95%:1.35-2.75) and haplotype frequencies (X2=13.93, p=0.003) between autistic patients and controls. The autistic patients showed higher frequencies of the Short (S) allele of 5-HTTLPR and the A / S haplotypes (rs25531 / 5-HTTLPR). We are currently analysing the expression level and the methylation status of the SLC6A4 gene in lymphoblastoïde cell lines from autistic patients carrying different genotypes for 5-HTTLPR (Long/Long, Long/Short, Short/Short). These experiments are performed on lymphoblastoïde cells cultured with or without brain neurotrophic factor (BDNF), molecule acting on the serotoninergic system.
Conclusions: Our results reinforce the implication of the gene encoding 5-HTT in autism vulnerability and suggest a direct role for the region carrying the Short allele of 5-HTTLPR.