COMT and MAO-A polymorphisms and obsessive-compulsive disorder: a family-based association study.

Aline Santos Sampaio,Eurípedes Constantino Miguel,Margaret Richter,Kátia Petribú,Ana Gabriela Hounie,Homero Vallada,Jesen Fargeness,Leonardo Fontenelle,James Kennedy,Carlos Alberto De Bragança Pereira,Paul Arnold,Gregory L Hanna,Ivanil Morais,Carolina Cappi,Maria Conceição Do Rosário,Carol Mathews,S Evelyn Stewart,David L Pauls

doi:10.1371/journal.pone.0119592

Abstract

ObjectiveObsessive-compulsive disorder (OCD) is a common and debilitating psychiatric illness. Although a genetic component contributes to its etiology, no single gene or mechanism has been identified to the OCD susceptibility. The catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A) genes have been investigated in previous OCD studies, but the results are still unclear. More recently, Taylor (2013) in a comprehensive meta-analysis of genetic association studies has identified COMT and MAO-A polymorphisms involved with OCD. In an effort to clarify the role of these two genes in OCD vulnerability, a family-based association investigation was performed as an alternative strategy to the classical case-control design.MethodsTransmission disequilibrium analyses were performed after genotyping 13 single-nucleotide polymorphisms (eight in COMT and five in MAO-A) in 783 OCD trios (probands and their parents). Four different OCD phenotypes (from narrow to broad OCD definitions) and a SNP x SNP epistasis were also analyzed.ResultsOCD, broad and narrow phenotypes,were not associated with any of the investigated COMT and MAO-A polymorphisms. In addition, the analyses of gene-gene interaction did not show significant epistatic influences on phenotype between COMT and MAO-A.ConclusionsThe findings do not support an association between DSM-IV OCD and the variants of COMT or MAO-A. However, results from this study cannot exclude the contribution of these genes in the manifestation of OCD. The evaluation of broader spectrum phenotypes could help to understand the role of these and other genes in the pathophysiology of OCD and its spectrum disorders.

Highlights

Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts and repetitive behaviors that are unwanted, time consuming, egodystonic, and result in significant functional impairment [1]
The findings do not support an association between DSM-IV OCD and the variants of COMT or monoamine oxidase A (MAO-A)
Various studies have demonstrated that the etiology of OCD has a genetic component [2] with reported heritability rates ranging between 27% and 65% [3]

Summary

Introduction

Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts (obsessions) and repetitive behaviors (compulsions) that are unwanted, time consuming, egodystonic, and result in significant functional impairment [1]. The etiology of OCD seems to involve an interaction between environmental factors and several genes of small effect [2]. Studies have reported dopaminergic abnormalities in the basal ganglia and nucleus accumbens, as well as altered glutamate transmission in other locations in OCD samples, suggesting that complex interactions between multiple neurotransmitter systems may contribute to the phenotypic presentation of OCD [6]. This could be understood by a potential dysfunction in enzymes that metabolize central nervous system neurotransmitters in OCD. Two important enzymes of this type are catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A)

Methods

Results

Conclusion