Association study between genetic monoaminergic polymorphisms and OCD response to clomipramine treatment

Abstract

In the present paper, we investigated the 5HTTLPR and STin2 polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4), the G861C polymorphism (rs6296) of the serotonin receptor 1D beta (HTR1B), the T102C (rs6113) and C516T (rs6305) polymorphisms of the serotonin receptor gene subtype 2A (HTR2A), the DAT UTR, DAT intron 8 and DAT intron 14 of the dopamine transporter gene (SLC6A3), the Val-158-Met (rs4680) polymorphism of the COMT and the silent mutation G1287A (rs5569) in the norepinephrine transporter gene (SLC6A2). We genotyped 41 obsessive-compulsive disorder (OCD) outpatients, classified as good-responders (n=27) and poor-responders (n=14) to treatment with clomipramine according to the Yale Brown Obsessive-Compulsive Scale (YBOCS). Patients who achieved a reduction in symptoms of 40% or more in YBOCS after 14 weeks of treatment were considered good-responders. Genotypes and alleles distribution of the investigated polymorphisms were compared between both groups. We did not find association between the studied polymorphisms and clomipramine response in our sample. Key words: OCD, clomipramine, serotonin receptor, serotonin transporter, dopamine transporter, norepinephrine transporter.Estudo de associação entre polimorfismos genéticos monoaminérgicos e resposta à clomipramina no tratamento do TOC RESUMO No presente estudo, investigaram-se os polimorfismos 5HTTLPR e STin2 da região promotora do gene transportador de serotonina (SLC6A4), o G861C (rs6296) do receptor de serotonina 1D beta (HTR1B), os polimorfismos T102C (rs6113) e C516T (rs6305) do gene do receptor da serotonina subtipo 2A (HTR2A), os polimorfismos UTR, intron 8 e intron 14 do gene transportador de dopamina (SLC6A3), o Val-158-Met (rs4680) da COMT e a mutação G1287A (rs5569) do gene do transportador de norepinefrina (SLC6A2). Foram genotipados 41 pacientes com transtorno obsessivo-compulsivo (TOC), classificados como bons-respondedores (n=27) e maus-respondedores (n=14) ao tratamento com clomipramina, por meio do uso da Escala de Sintomas Obsessivos-Compulsivos Yale Brown (YBOCS). Foram considerados bons-respondedores os pacientes que tiveram redução nos sintomas em 40% ou mais na YBOCS, após 14 semanas de tratamento. A distribuição dos genótipos e alelos estudados foi comparada entre os dois grupos. Não foi encontrada associação entre estes polimorfismos investigados e a resposta à clomipramina na amostra estudada. Palavras-chave: TOC, clomipramina, receptor serotonérgico, transportador de serotonina, transportador de dopamina, transportador de norepinefrina.

Endophenotypes and serotonergic polymorphisms associated with treatment response in obsessive-compulsive disorder

“…Those results suggested that the C516T variant of the HTR2A gene may be a genetic risk factor for OCD. Another study by our group found no association between the 5HTTLPR and STin2 polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4), the G861C polymorphism (rs6296) of HTR1B, the T102C (rs6113) and C516T (rs6305) polymorphisms of HTR2A and the clomipramine response in OCD patients (19). In the present study, these divergences may be caused by differences in sample characteristics with the refractory patients in the RT group and the highly responsive patients in the RP group.…”

No association between the COMT Val158Met polymorphism and the long‐term clinical response in obsessive–compulsive disorder in the Japanese population

“…Two other studies examined the association between the COMT Val158Met polymorphism and clinical responses in OCD. Miguita and colleagues () compared a group of good responders to a group of poor responders to clomipramine, a tricyclic antidepressant, and an SRI for 14 weeks in OCD ( N = 41) and did not find significant associations between this polymorphism and clinical response (Miguita et al . ).…”

“…Two other studies examined the association between the COMT Val158Met polymorphism and clinical responses in OCD. Miguita and colleagues (2011) compared a group of good responders to a group of poor responders to clomipramine, a tricyclic antidepressant, and an SRI for 14 weeks in OCD (N = 41) and did not find significant associations between this polymorphism and clinical response (Miguita et al 2011). Vulink and colleagues (2012) examined whether the COMT Val158Met polymorphism reduces the efficacy of adding quetiapine to citalopram, an SSRI with an atypical antipsychotic, for 10 weeks in OCD (N = 64) (Vulink et al, 2012).…”

“…). Moreover, the two pharmacogenetic studies that examined the associations between the COMT Val158Met polymorphism and clinical response to serotonin reuptake inhibitors (SRI) in OCD likewise failed to produce consistent results (Miguita et al ., ; Vulink et al ., ).…”

“…To date, several genetic case-control association studies between the COMT Val158Met polymorphism and OCD have been performed in various populations, and the results of these association studies are not consistent (Karayiorgou et al, 1997;Ohara et al, 1998;Niehaus et al, 2001;Erdal et al 2003;Meira-Lima et al, 2004;Poyurovsky et al, 2005;Denys et al, 2006;Pooley et al, 2007;Katerberg et al, 2010;Tükel et al, 2013). Moreover, the two pharmacogenetic studies that examined the associations between the COMT Val158Met polymorphism and clinical response to serotonin reuptake inhibitors (SRI) in OCD likewise failed to produce consistent results (Miguita et al, 2011;Vulink et al, 2012).…”