Association of 5ht2a (RS6313) and serotonine transporter protein gene (5HTT/RS25531) polymorphisms with treatment response in clomipramine-treated patients

Aim: This study aims to explore the potential association between serotonin receptor gene polymorphisms and clomipramine treatment response and side effects profile in treatment-resistant OCD patients. The hypotheses of this thesis study are that (i) HTR2A gene T102C (rs6313) and SLC6A4 gene 5-HTTLPR variation and rs25531 polymorphisms are associated with treatment response in clomipramine-trated treatment-resistant OCD patients (ii) need for cognitive closure is associated with HTR2A rs6313 and SLC6A4 5HTTLPR and rs25531 polymophisms in treatment-resistant OCD patients (iii) Clomipramine side effects are associated with HTR2A rs6313, SLC6A4 5HTTLPR and rs25531 polymorphisms in treatment-resistant OCD patients. Materials and methods: 64 patients with treatment-resistant OCD diagnosis were enrolled in this study and Yale Brown Obsessive Compulsive Scale was used for assessment of OCD severity. Hamilton Depression Scale, Need For Closure Scale –Short Version (15-item) were administered. 56 patients who agreed to provide blood sample were evaluated with UKU side effect assessment scale and genotyped for HTR2A rs6313, SLC6A4 5-HTTLPR and rs25531 polymorphisms. Results: No correlation was detected between HTR2A T102C polymorhism and clinical features, severity or clomipramine treatment response of OCD. Age of onset of OCD was associated with L allele in 5-HTTLPR polymorhism. S allele was related with history of tic disorder in the same polymorphism. For rs25531, there was a stronger relationship between LA allele and age of onset of OCD. There were no relationship between clomipramine induced side effects and HTR2A gene T102C polymorphism. Tremor, increased sweating and diminished sexual desire were found to be related to 5-HTTLPR polymorphism. In rs25531 polymorphism, there was a relationship between LA allele absence and incread sweating as a side effect of clomipramine. There were no relationship between need for cognitive closure and clinical features or severity of OCD, but there was an inverse relationship between need for cognitive closure and OCD tratment response. Order factor of need for cognitive closure was associated with 5-HTTLPR S allele presence and intolerance for uncertainty, another factor of need for cognitive closure, was associated with C allele presence in HTR2A T102C polymorphism. Conclusions: These findings suggest that HTR2A and SLC6A4 genes may influence some aspects of OCD phenotype but not the response to clomipramine treatment. Some of the side effects that associated with clomipramine might be associated with HTR2A and SLC6A4 polymorphisms. Need for cognitive closure was not associated with clinical features and severity of OCD but it might be a predictor of the treatment response in OCD patients. Key words: obsessive compulsive disorder, genetic polymorphism, clomipramine, side effect, need for cognitive closure