Association of Serotonin Transporter Gene Polymorphisms with Obsessive-Compulsive Disorder (OCD) in a South Indian Population (Report‪)‬

Obsessive compulsive disorder (OCD) is the fourth most prevalent psychiatric disorder with a lifetime prevalence of 2-3 per cent (1). It is often a chronic illness characterized by obsessional thoughts and/or compulsive acts (2). Although OCD is often considered a unitary disorder, there is evidence that it is a heterogeneous disorder (3). Juvenile OCD and tic related OCD are considered to be valid subtypes (4-6). Good therapeutic efficacy of serotonin reuptake inhibitors (SRIs) in OCD (7,8) has prompted search for association between OCD and variations in the SLC6A4 gene. A functional polymorphism in the 5' regulatory promoter region 5-HTTLPR (5-HTT gene-linked polymorphic region), involving two common alleles that correspond to a 43-base pair insertion (L allele) or deletion (S allele), has been reported (9). The S allele of 5-HTTLPR polymorphism reduces transcription efficiency for the SLC6A4 gene, resulting in decreased gene expression, and thus, decreased serotonin uptake in lymphoblast cell lines (10). Recent research shows varied results with respect to association between 5-HTTLPR alleles and OCD. In a meta-analysis by Lin (11), only two studies (12,13) showed a significant association of LL genotype with OCD. The overall result of the meta-analysis demonstrated an association of OCD with SS genotype and a reverse association with L/S genotype. Denys et al (14), found an association of S allele of 5-HTTLPR with female OCD patients. However, Dickel et al (15), supported a nominally significant over-transmission of the L allele in female patients. A recent meta-analysis suggests the possibility that the L allele may be associated with OCD in specific subgroups such as childhood-onset OCD, and in Caucasians (16).