Association of the SLC1A1 glutamate transporter gene and obsessive-compulsive disorder

Am J Med Genet B Neuropsychiatr Genet. 2007 Dec 5;144B(8):1027-33. doi: 10.1002/ajmg.b.30533.

Abstract

Context: Obsessive-Compulsive Disorder (OCD) is a debilitating illness with putative glutamatergic abnormalities. Two separate proximal haplotypes in the glutamate transporter gene, SLC1A1, were recently reported to be associated with OCD among males, but replication is required.

Objectives: This study examines SLC1A1 as a candidate gene for OCD and explores gender influences. It was hypothesized that a significant association between SLC1A1 and OCD would be replicated in an independent sample of males but not females.

Design: Family-based association candidate gene study.

Setting: Participants were recruited from tertiary care OCD specialty clinics.

Participants: OCD probands and their first degree relatives.

Main outcomes measures: Association of OCD with genotypes of single nucleotide polymorphism (SNP) markers and related haplotypes.

Results: Association between OCD and the three-marker haplotype rs12682807/ rs2072657/ rs301430, with overtransmission of A/T/T, was observed in both genders combined (global P = 0.0015) and in males (global P = 0.0031). Single-marker associations with OCD in the region (rs3780412 and rs2228622) demonstrated modest significance (permuted P = 0.045).

Conclusions: This study identifies a significant association between the SLC1A1 glutamate transporter gene and OCD in a haplotype overlapping with that recently reported.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Distribution
  • Age of Onset
  • Child
  • Chromosome Mapping
  • Excitatory Amino Acid Transporter 3 / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Obsessive-Compulsive Disorder / diagnosis
  • Obsessive-Compulsive Disorder / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Sex Distribution

Substances

  • Excitatory Amino Acid Transporter 3
  • SLC1A1 protein, human