Transmission disequilibrium studies in early onset of obsessive-compulsive disorder for polymorphisms in genes of the dopaminergic system

J Neural Transm (Vienna). 2008 Jul;115(7):1071-8. doi: 10.1007/s00702-008-0051-6. Epub 2008 Apr 30.

Abstract

The dopaminergic system has been shown to be involved in the aetiology of obsessive-compulsive disorder (OCD). Family studies suggest a higher genetic loading in patients with early onset OCD. Our investigation is the first family-based association study concerning polymorphisms in genes of the dopaminergic system in early onset OCD. We studied polymorphisms within the dopamine-4 receptor gene (DRD4), the dopamine transporter gene (DAT1) and the catecholamine-O-methyltransferase gene (COMT). Associations of alleles of DRD4 and COMT with OCD have previously been reported in adults, while a trend towards an association was found for DAT1 alleles. In our study we observed transmission disequilibrium for the 48-bp repeat polymorphism of the DRD4 gene using the ETDT (P=0.047) in 69 trios comprising patients with early onset OCD and both of their parents. Post hoc TDT analysis of the DRD4 showed reduced transmission of the 4-repeat allele and a slightly increased transmission rate for the 7- and the 2-repeat allele. No evidence of transmission disequilibrium was detected for alleles of the DAT1 and COMT polymorphisms. These polymorphisms do not appear to play a major role in the genetic predisposition to early onset OCD in our study group.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Catechol O-Methyltransferase / genetics*
  • Child
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Linkage Disequilibrium*
  • Male
  • Obsessive-Compulsive Disorder / genetics*
  • Polymorphism, Genetic*
  • Receptors, Dopamine D4 / genetics*

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • SLC6A3 protein, human
  • Receptors, Dopamine D4
  • Catechol O-Methyltransferase