Association study of two SLC6A4 polymorphisms with autism.

Abstract

INTERDISCIPLINARY STUDIES: NEUROGENETICS

ASSOCIATION STUDY OF TWO SLC6A4 POLYMORPHISMS WITH AUTISM

JACQUELYN RECKTENWALD

Thesis under the direction of Professor James Sutcliffe Autism is a heritable neurodevelopmental disorder characterized by impairments in language development and use, social interaction and repetitive behaviors, restricted interests and resistance to change. Serotonergic system dysregulation is implicated in autism since ~25% of individuals with autism have blood platelet hyperserotonemia, selective serotonin reuptake inhibitors are efficacious in treating repetitive behaviors, anger and anxiety in autism, and PET studies indicate children with autism have less capacity for CNS serotonin synthesis than children without autism. These findings indicate the serotonin transporter (SERT) as a strong candidate susceptibility gene and studies point toward linkage in a region containing the SERT gene (SLC6A4) locus with autism. Two SLC6A4 repeat polymorphisms, HTTLPR and VNTR, are located in the promoter region upstream of SLC6A4 and in the second intron, respectively, and regulate SERT expression. Association studies of HTTLPR or VNTR polymorphisms with autism are inconclusive. We hypothesized that there would be preferential transmission of an HTTLPR polymorphism, VNTR polymorphism and a haplotype containing these polymorphisms to affected individuals in our sample. We found no association of any HTTLPR polymorphisms or VNTR polymorphisms with autism in our sample and further we did not find any association of a haplotype containing these polymorphisms with autism in our sample. Paternal inheritance of VNTR alleles was associated with the social intent and milestones (p =.02 and p = .05, respectively) components of the ADI-R, however, these two association results may be due to chance.