Genetic and pharmacogenetic study of glutamate transporter (SLC1A1) in Iranian patients with obsessive-compulsive disorder

Abstract

Summary What is known and objective Obsessive‐compulsive disorder (OCD) is a chronic neuropsychiatric disorder. Selective serotonin reuptake inhibitors (SSRIs) are the first line of medication for OCD treatment; however, 40%‐60% of patients with OCD do not respond to SSRIs adequately. There are growing pieces of evidence which suggest a significant role for the glutamatergic system in the genesis of OCD and its consequent treatment. In the present study, we aimed to assess the association of SLC1A1 polymorphisms (rs301430, rs2228622 and rs3780413) with OCD and its clinical characteristics, as well as the importance of these SNPs in the response of OCD patients to SSRI pharmacotherapy. Methods Sample study consisted of 243 OCD cases and 221 control subjects. Patients were treated 12 weeks with fluvoxamine (daily dose: 150‐300 mg). Based on the reduction in obsessive and compulsive severity scores using Y‐BOCS severity scale, patients were classified as responders, non‐responders and refractory. A total of 239, 228 and 215 patients were genotyped for rs301430, rs2228622 and rs3780413, respectively, by the means of PCR‐RFLP. Results and discussion 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 results of pharmacogenetic studies revealed the associations of two SLC1A1 SNPs, rs2228622 (P = 0.031) and rs3780413 (P = 0.008), with treatment response. What is new and conclusion Results of the current study suggest a role for the glutamate transporter in OCD treatment response with SSRIs which should encourage researchers to further investigate the importance of glutamate transporter in OCD pharmacogenetics.

SLC1A1, SLC16A9, and CNTN3 Are Potential Biomarkers for the Occurrence of Colorectal Cancer

“…The downregulated hub gene SLC1A1 (solute carrier family 1, member 1) is located on chromosome 9p24 and encodes for a member of the high-affinity glutamate aspartate transporter family, which is essential for the transport of glutamate across plasma membranes [49]. The studies related to SLC1A1 have most commonly involved the investigation of neuropsychiatric disorders [50,51]. There have been few studies investigating the relationship between SLC1A1 expression and cancer.…”

Association of SAPAP3 allelic variants with symptom dimensions and pharmacological treatment response in obsessive–compulsive disorder.

“…A large GWAS which examined treatment response in OCD (Qin et al, 2016), found a locus in DLGAP1 and multiple other genes in the glutamatergic signaling pathway (Enrichment score = 3.38, FDR=0.00097) to be associated with SRI resistance. Two studies with a candidate gene approach that have examined the association between SLC1A1 SNPs and treatment response (Abdolhosseinzadeh et al, 2019;Real et al, 2013) have also found an association with treatment resistance. Recently, a study using a polygenic risk score with all the above-mentioned variants (Alemany-Navarro et al, 2019) failed to find any association between the composite score and treatment response in OCD.…”

Comprehensive Analysis of Potential Correlation Between Solute Carrier 1A (SLC1A) Family and Lung Adenocarcinoma

“…The studies of SLC1A1 have widely participated in neuropsychiatric disorders. 34 , 35 The article showed that the expression of SLC1A1 in clear cell renal cell carcinoma tissues significantly increased than normal kidney tissues, and was higher in males than females. 36 Bianchi et al, reported that high-expressed SLC1A1 was associated with the differentiation of glioma cells.…”