Association of Val158Met polymorphism in COMT gene with attention-deficit hyperactive disorder

Abstract

Background: The results of published articles on the relationship between the Val158Met polymorphism in the (Catechol-O-methyltransferase) COMT gene and the susceptibility of attention-deficit hyperactive disorder (ADHD) are controversial. We conducted an updated meta-analysis of case-control studies to assess the relationship between Val158Met polymorphism in COMT gene and ADHD susceptibility. Methods: A comprehensive literature search was conducted to identify all the case-control studies on the relationship between the COMT gene Val158Met polymorphism and ADHD susceptibility. According to the heterogeneity test results among studies evaluated with I 2 , the fixed effect model or random effect model was selected as the pooling method. Meta-regression as well as sensitive analysis were used to explore possible causes of between-study heterogeneity. The funnel plot and Harbord test were used to estimate publication bias. Results: Finally, seventeen studies that met the inclusion criteria were included. The Val158Met genotype distributions of COMT gene in controls were in Hardy–Weinberg equilibrium in all studies. In general, there was no significant association between the COMT gene Val158Met polymorphism and ADHD susceptibility in dominant, recessive, and codominant models. The recessive genetic model ( I 2 = 60.8%) showed strong heterogeneity among studies, and still no significant association was found after sensitivity analysis. Subgroup analysis stratified by ethnicity (Asian and Caucasian) also showed that there was no significant association in the above-mentioned three models. Conclusions: This updated meta-analysis indicated that the Val158Met polymorphism in the COMT gene may not be related to the risk of ADHD. Further researches are needed to confirm these results.

The Role of Iron and Zinc in the Treatment of ADHD among Children and Adolescents: A Systematic Review of Randomized Clinical Trials

“…Etiological research outlines that ADHD constitutes a complex condition with multiple interactive factors [9]. Specific causes of the disorder are yet to be determined, but various contributing risk factors have been identified, including genetics [10][11][12][13], epigenetics [14,15], problems during pregnancy (such as stress, substance use, and other mental and physical diseases) [16][17][18], premature birth [19,20], obstetric and neonatal complications [21][22][23][24], and infections [25,26]. Neuropsychological mechanisms have also been identified in the onset and course of ADHD, such as brain injuries [27], neuroanatomical substrates related with genuine motor dysfunction [28] and deficient decision-making [29].…”

A mechanistic model of ADHD as resulting from dopamine phasic/tonic imbalance during reinforcement learning

“…COMT haplotypes showed different level of activity (Diatchenko et al, 2005 ; Nackley et al, 2006 ) and it has been proposed that a decrease in COMT activity in the PFC could increase firing of pyramidal neurons and glutamate transmission in basal ganglia, leading to an increase in tonic dopamine, which in turn results in a decrease in phasic dopamine (Bilder et al, 2004 ). However, this model has yet to be convincingly proven (Nolan et al, 2004 ; Rosa et al, 2010 ), as the association of genetic variants of COMT with ADHD (Kang et al, 2020 ). In our model, dopamine phasic release decreases with autoreceptor occupancy (Benoit-Marand et al, 2001 ).…”

Prevalence of Common Alleles of Some Stress Resilience Genes among Adolescents Born in Different Periods Relative to the Socioeconomic Crisis of the 1990s in Russia

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