Association of two specific haplotypes of serotonin transporter gene with fluvoxamine treatment outcomein Iranian patients with obsessive compulsive disorder

Introduction: Converging lines of evidence indicate that serotonin transporter has a role in response to selective serotonin reuptake inhibitors pharmacotherapy in a variety of neuropsychiatric disorders. In the present study, the association of four functional loci of the serotonin transporter gene (SLC6A4) with fluvoxamine treatment outcome in Iranian patients with obsessive compulsive disorder (OCD) has been investigated. Methods: A total of 352 Iranian OCD patients were screened for the treatment outcome. Pharmacotherapy was defined as 12 weeks of treatment with fluvoxamine (150-300mg). Finally, 132 patients who had completed their treatment were assigned to three groups (responders, non-responders and refractory) and underwent genotyping for SLC6A4 variations (STin2, 5-HTTLPR, rs25531 and rs25532) employing PCR-RFLP. Results: Results showed no significant differences between different STin2, 5-HTTLPR/ rs25531 and rs25532 single locus genotype frequencies. However, significant associations of two SLC6A4 haplotypes with treatment response were detected. Conclusion: Detected association of two SLC6A4 haplotypes with response to fluvoxamine in OCD patients proposed that the research emphasis of OCD pharmacogenetic studies may be placed on haplotype association analyses in candidate genes. This may represent a significant advance over single-locus investigations as a way to understand the influence of genetic factors on drug response in OCD.