Role of the serotonin transporter gene in the behavioral expression of autism.
The promoter polymorphism of the serotonin transporter gene (HTT, locus SLC6A4) is of special interest in autism given the well-replicated platelet hyperserotonemia of autism, treatment effects of serotonin reuptake inhibitors, and the role of serotonin in limbic functioning and neurodevelopment. Parent-offspring transmission of the long (l) and short (s) alleles of the deletion/insertion polymorphism in the HTT promoter region was examined in families of 71 children with autism using the transmission test for linkage disequilibrium (TDT). Transmission of HTT promoter alleles did not differ between probands with autism and their unaffected siblings. However, allelic transmission in probands was dependent upon severity of impairments in the social and communication domains, with greater s allele transmission in severely impaired individuals and greater l transmission in mild/moderately impaired individuals. This relationship between HTT promoter alleles and severity of autistic impairment was also seen when ratings of social and communication behaviors were compared across genotypes. The data indicate that HTT promoter alleles by themselves do not convey risk for autism, but, rather, modify the severity of autistic behaviors in the social and communication domains. The results require replication and, given the size of the groups and subgroups examined, must be considered still preliminary. The results suggest that future research on the genetics of autism should carefully assess each of the major behavioral domains and seriously consider the possible role of modifying loci.
Tordjman
S
S
FRE 2134 CNRS Genetics Neurogenetics and Behavior, 3B Férollerie Street, 45071 Orléans cedex 2, France. lubart@idf.jussieu.fr
Gutknecht
L
L
Carlier
M
M
Spitz
E
E
Antoine
C
C
Slama
F
F
Carsalade
V
V
Cohen
D J
DJ
Ferrari
P
P
Roubertoux
P L
PL
Anderson
G M
GM
D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000235:genetics* / Q000523:psychology; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D004251:DNA Transposable Elements; D005220:Fathers; D005260:Female; D005602:France; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009035:Mothers; D009419:Nerve Tissue Proteins; D009679:Nuclear Family; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D050486:Serotonin Plasma Membrane Transport Proteins; D014888:Wechsler Scales; D044465:White People / Q000235:genetics
D002352:Carrier Proteins; D004251:DNA Transposable Elements; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins