To test for association between SLC1A1 and autism, we typed three single nucleotide polymorphisms (SNPs, rs301430, rs301979, rs301434) previously associated with OCD in 86 strictly defined trios with autism.
The glutamate transporter gene SLC1A1, which was recently reported to be associated with obsessive-compulsive disorder (OCD), is a promising candidate gene for susceptibility to AAP-induced OC symptoms.
As several other uncommon, less well quantitated genetic variations occur with an OCD phenotype, including chromosomal anomalies and some other rare gene variants (SGCE, GCH1 and SLITRK1), a tentative conclusion is that OCD resembles other complex disorders in being etiologically heterogeneous and in having both highly penetrant familial subtypes associated with rare alleles or chromosomal anomalies, as well as having a more common, polygenetic form that may involve polymorphisms in such genes as BDNF, COMT, GRIN2beta, TPH2, HTR2A and SLC1A1.
To determine the role of genetic variation of SLC1A1 in OCD in a large case-control study and to better understand how SLC1A1 variation affects functionality.
We aimed to assess whether genetic variants in SLC1A1 and life stress at onset of the disorder interact and modulate pharmacological resistance in OCD.
No association was detected between SLC1A1 SNPs and OCD, except an association between the familial form of the disease in males with rs2228622 (P = 0.033).
The C-T-G haplotype at rs301430-rs301434-rs3087879 of SLC1A1 was significantly associated with higher PD scores after adjusted for age, sex, and OCD status.
This mini-review summarizes recent findings regarding the neurobiological basis of OCD, with an emphasis on the glutamatergic neurotransmission and EAAT3 as a key player in OCD etiology.
Findings of this meta-analysis are consistent with the trend of previous candidate gene studies in psychiatry and do not clarify the putative role of SLC1A1 in OCD pathophysiology.
Although of nominal statistical significance considering the number of comparisons, these findings provide further support for the involvement of SLC1A1 in the pathogenesis of OCD.
SLC1A1, a glutamate transporter gene on chromosome 9p, was originally proposed to be related to OCD based on two linkage studies, and subsequently association of OCD to the gene has been replicated.