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Association analyses reveal gender-specific associations of DAT1 40-bp VNTR and -839C/T polymorphisms with obsessive–compulsive disorder and obsessive–compulsive symptoms

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Abstract

The dopamine transporter (DAT) is involved in dopamine signaling and distribution, controlling dopamine concentrations and contributing to several central nervous system disorders. The purpose of this study was to determine the association between two functional polymorphisms in DAT1 gene, the 40-base pair Variable Number of Tandem Repeats (VNTR) and the Single Nucleotide Polymorphism (SNP) -839C/T and obsessive–compulsive disorder (OCD) and/or its clinical features. To do so, 199 OCD patients and 201 healthy controls were genotyped using Polymerase Chain Reaction (PCR). Genotype distribution of both polymorphisms was in Hardy–Weinberg equilibrium. Although OCD and controls did not differ in terms of polymorphisms distribution, we observed that the presence of 10R-allele protected men of having OCD (P = 0.03). We also observed a significant association between the presence of 10R and checking in women (P = 0.02; OR = 3.14; 95%CI 1.08–9.11), and between the 9/9 genotype and neutralization in men (P = 0.04; OR = 3.38; 95%CI 1.03–11.11). Finally, the T-allele of -839C/T was significantly associated with the “obsession” score (P = 0.02; OR = 2.66; 95%CI 1.15–6.13). Our results demonstrate an important influence of dopaminergic pathways, particularly DAT1 polymorphisms, in OCD.

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Acknowledgements

We wish to thank all patients and healthy controls who volunteered to participate in this study, and to all their relatives. We also thank the support of Isabele Gomes Giori, Fernanda Melo-Felippe, and Tamiris Vieira-Fonseca in sample collection and DNA isolation. This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, Brazil), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Pró-Reitoria de Pesquisa, Pós-Graduação e Inovação from Universidade Federal Fluminense (Proppi/PDI/UFF).

Funding

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil; Grant Number 477658/2009-1 and 472033/2012-3), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, Brazil; Grant Number E-26/110.080/2010 and E-26/111.751/2012), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Pró-Reitoria de Pesquisa, Pós-Graduação e Inovação from Universidade Federal Fluminense (Proppi/PDI/UFF). The funding source(s) had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

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Authors and Affiliations

  1. Programa de Pós-Graduação em Ciências e Biotecnologia, Universidade Federal Fluminense (UFF), Niterói, Brazil

    Juliana C. Cotrin & Fabiana B. Kohlrausch

  2. Programa de Obsessões, Compulsões e Fobias, Instituto de Psiquiatria, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

    Leonardo F. Fontenelle

  3. Instituto D’Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, Brazil

    Leonardo F. Fontenelle

  4. School of Psychological Sciences, MONASH University, Melbourne, Australia

    Leonardo F. Fontenelle

  5. Departamento de Biologia Geral, Instituto de Biologia, UFF, Niterói, RJ, 24061-970, Brazil

    Fabiana B. Kohlrausch

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  1. Juliana C. Cotrin
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  2. Leonardo F. Fontenelle
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Correspondence to Fabiana B. Kohlrausch.

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Cotrin, J.C., Fontenelle, L.F. & Kohlrausch, F.B. Association analyses reveal gender-specific associations of DAT1 40-bp VNTR and -839C/T polymorphisms with obsessive–compulsive disorder and obsessive–compulsive symptoms. Mol Biol Rep 46, 5155–5162 (2019). https://doi.org/10.1007/s11033-019-04971-9

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