Functional studies and rare variant screening of SLC1A1/EAAC1 in males with obsessive-compulsive disorder

Psychiatr Genet. 2012 Oct;22(5):256-60. doi: 10.1097/YPG.0b013e328353fb63.

Abstract

Several studies have found that the neuronal glutamate transporter gene SLC1A1/EAAC1 is associated with obsessive-compulsive disorder (OCD), with a stronger association in males. Previous studies have primarily focused on common single-nucleotide polymorphisms, rather than rare functional variants that are likely to have larger effects. We screened 184 males with OCD for rare variation in SLC1A1 exons; however, no new coding variation was found. When combined with previous screens, only one SLC1A1 amino acid variant has been detected among the 841 individuals screened, which is less than for other neurotransmitter transporter genes (P=0.0001). We characterized the function of the one SLC1A1 missense variant reported previously in OCD, Thr164Ala, and found that the Ala164 allele leads to decreased Vmax and Km (P<0.0001) in transfected human embryonic kidney cells. Further work will be necessary to understand the impact of this rare SLC1A1/EAAC1 Ala164 variant on neuronal function and circuitry relevant to OCD.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Excitatory Amino Acid Transporter 3 / genetics*
  • Genetic Predisposition to Disease*
  • Genetic Testing*
  • Glutamic Acid / metabolism
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Obsessive-Compulsive Disorder / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Sequence Analysis, DNA
  • Young Adult

Substances

  • Excitatory Amino Acid Transporter 3
  • SLC1A1 protein, human
  • Glutamic Acid