Association analysis between a VNTR intron 8 polymorphism of the dopamine transporter gene (SLC6A3) and obsessive- compulsive disorder in a Brazilian sample

Abstract

-Family, twin and segregation analysis have provided evidences that genetic factors are implicated in the susceptibility for obsessive-compulsive disorder (OCD). Several lines of research suggest that the dopaminergic system may be involved in the pathophysiology of OCD. Thus, the aim of the present study was to investigate a possible association between a polymorphism located in intron 8 of the dopamine transporter gene (SLC6A3) and OCD in a Brazilian sample composed by 208 patients and 865 healthy controls. No statistically differences were observed in allelic and genotype distributions between cases and controls. No association was also observed when the sample was divided according to specific phenotypic features such as gender, presence of tic disorders co-morbidity and age at onset of obsessive-compulsive symptoms (OCS). Our results suggest that the intron 8 VNTR of the SLC6A3 investigated in this study is not related to the susceptibility for OCD in our Brazilian sample.KEY WORDS: dopamine, obsessive-compulsive disorder, genetic association, DAT1, allele, genotype. Análise de associação entre um polimorfismo VNTR no intron 8 do gene do transportador de dopamina (SLC6A3) e transtorno obsessivo-compulsivo em uma amostra brasileiraRESUMO -Estudos de família, gêmeos e de segregação têm demonstrado que fatores genéticos estão envolvidos na susceptibilidade para o desenvolvimento do transtorno obsessivo-compulsivo (TOC). Várias linhas de pesquisa sugerem que o sistema dopaminérgico possa estar envolvido na fisiopatologia do TOC. Assim, o objetivo do presente estudo foi investigar uma possível associação entre o polimorfismo localizado no intron 8 do gene do transportador da dopamina (SLC6A3) e o TOC em uma amostra brasileira composta por 208 pacientes e 865 controles sadios. Nenhuma diferença estatisticamente significante foi observada nas distribuições alélicas e genotípicas entre os grupos de pacientes e controles. Nenhuma associação também foi observada quando as amostras foram divididas de acordo com características fenotípicas específicas, tais como gênero, presença de co-morbidade com tiques e idade de início dos sintomas obsessivocompulsivo (SOC). Nossos resultados sugerem que o VNTR do intron 8 investigado neste estudo não está relacionado com o TOC na nossa amostra brasileira.

Gender differences in obsessive-compulsive disorder: a literature review

“…53 This genetic link, supporting the association of the dopaminergic system with the pathophysiology of OCD and a dimorphic pattern due to gender, was not found while investigating the association between the polymorphism located in the intron 8 of the dopamine transporter gene (SLC6A3 or DAT1) and OCD in a Brazilian sample of 208 patients and 865 healthy controls. 65 The positive finding of needs replication as it is difficult to interpret: the association of the A2 allele with the OCD sample was unexpected and the A1 allele of the DRD2 TaqI A system has been found to be associated with a variety of addictive, impulsive, and compulsive disorders.…”

A review of psychiatric genetics research in the Brazilian population

“…Miguita et al investigated the 1287 A/G NET and VNTR DAT1 polymorphisms; however, they did not find an association with OCD. 45,46 Based on the several lines of evidence supporting an immunologic involvement on OCD etiopathogenesis, Hounie et al investigated polymorphisms of the promoter region of the TNF-alpha gene and association of the -308 G/A and -238 G/A polymorphisms with the disorder. 47 The Program of the ObsessiveCompulsive Spectrum Disorders (PROTOC) at the Universidade de São Paulo Medical School has conducted genetic studies on families.…”

Genetic and epigenetic architecture of Obsessive-Compulsive Disorder: In search of possible diagnostic and prognostic biomarkers

“…A recent study found that the presence of at least one 10 repeats (10R) allele in the genotype of the SLC6A3 VNTR has a protective role against OCD in males (Cotrin et al, 2019). Several studies failed to replicate the association between the same polymorphism and the disorder (Billett et al, 1998;Frisch et al, 2000;Hemmings et al, 2003;Miguita et al, 2007Miguita et al, , 2011Taylor, 2013;Walitza et al, 2008;. Rs27072, a SNP in SLC6A3 gene, was positively correlated with OCD severity (Mas et al, 2016).…”