Gene variations in PBX1, LMX1A and SLITRK1 are associated with obsessive-compulsive disorder and its clinical features.

Genetic factors probably influence OCD development and a current hypothesis proposes that genes involved in the development of the central nervous system (CNS) are related to OCD. The aim of this study was to analyze six Single Nucleotide Polymorphisms (SNPs) in five genes with functions related to neurodevelopment in OCD. A total of 203 patient and 203 control samples were genotyped using the TaqMan® methodology. Statistically significant associations between OCD and PBX1 (rs2275558) in total sample (P = 0.002) and in males (P = 0.0003) were observed. Concerning symptom dimensions, the expression of neutralization showed a statistical significant association with LMX1A (rs4657411, P = 0.004) in total sample. We also observed significant association between LMX1A (rs4657411) and washing dimension in females (P = 0.01). Additionally, SLITRK1 (rs9593835) was significantly associated with checking dimension in male patients (P = 0.04). Our results indicate an important influence of neurodevelopment genes in the OCD susceptibility. Additional studies with larger samples are needed to confirm these results.

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

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.