Glutamate transporter gene polymorphisms and obsessive-compulsive disorder: A case-control association study

Abstract

The etiology of obsessive–compulsive disorder (OCD) is largely unknown, but family, twin, neuroimaging, and pharmacological studies suggest that glutamatergic system plays a significant role on its underlying pathophysiology. We performed an association analysis of six Single Nucleotide Polymorphisms (SNPs) within SLC1A1 gene (rs12682807, rs2075627, rs3780412, rs301443, rs301430, rs301434) in a group of 199 patients and 200 healthy controls. Symptom profiles were evaluated using the Florida Obsessive-Compulsive Inventory (FOCI) and the Obsessive-Compulsive Inventory-Revised (OCI-R). SNPs were analyzed by Taqman® methodology (Thermo Fisher, Brazil). The genotype distributions were in Hardy-Weinberg equilibrium. The A-A-G (rs301434-rs3780412-rs301443) haplotype was twice as common in OCD as in controls (P = 0.02). We also found significant differences between male patients and controls for rs301443 in a dominant model (P = 0.04) and a protective effect of GG genotype of rs2072657 in women (P = 0.02). Regarding clinical characteristics, the G-A (rs301434-rs3780412) haplotype was almost twice more common in patients with vs. without hoarding (P = 0.04). Further analyses showed significant associations between hoarding and rs301434 (P = 0.04) and rs3780412 (P = 0.04) in women, both in a dominant model. A dominant effect was also observed on ordering dimension for rs301434 (P = 0.01, in women) and rs301443 (P = 0.04). Finally, the rs2072657 showed a recessive effect on neutralization (P = 0.04) and checking (P = 0.03, in men). These preliminary results demonstrated that the SLC1A1 may contribute to some extent the susceptibility to OCD and its symptoms. However, additional studies are still needed.