Association of the COMT synonymous polymorphism Leu136Leu and missense variant Val158Met with mood disorders

Pandolfo, Gianluca; Gangemi, Chiara; Arrigo, Rosa; Currò, Monica; Ciura, Giulia La; Muscatello, Maria Rosaria Anna; Bruno, Antonio; Zoccali, Rocco Antonio; Caccamo, Daniela

doi:10.1016/j.jad.2015.02.016

Cited by 8 publications

(8 citation statements)

References 36 publications

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“…Numerous studies have examined the relation between MDD and COMT Val158Met (Kunugi et al 1997;Ohara et al 1998;Frisch et al 1999;Massat et al 2005;Arias et al 2006;Garriock et al 2006;Serretti et al 2006;Jabbi et al 2007;Huuhka et al 2008;Zalsman et al 2008;Potter et al 2009;Massat et al 2011;Opmeer et al 2013;Chiesa et al 2014;Hayashi et al 2014;Shen et al 2014;Wang et al 2014;Pandolfo et al 2015), but the results remain inconclusive. Massat and colleagues found a higher Val allele frequency in early-onset MDD (Massat et al 2005;Massat et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Meta-Analysis of the COMT Val158Met Polymorphism in Major Depressive Disorder: Effect of Ethnicity

Wang

Yuan

et al. 2016

J Neuroimmune Pharmacol

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The COMT (catechol-O-methyltransferase) Val158Met polymorphism (rs4680) is a potential susceptibility variant for major depressive disorder (MDD). Although many genetic studies have examined the association between MDD and this polymorphism, the results were inconclusive. In the present study, we conducted a series of meta-analyses of samples consisting of 2905 MDD cases and 2403 controls with the goal of determining whether this variant indeed has any effect on MDD. We revealed a significant association in the comparison of Val/Val + Val/Met vs. Met/Met (OR =1.180; 95 % CI = 1.019, 1.367; P = 0.027), Val/Met vs. Val/Val (OR =1.18; 95 % CI = 1.038, 1.361; P = 0.013), and Val/Met vs. Met/Met (OR =1.229; 95 % CI = 1.053, 1.435; P = 0.009). Further meta-analyses of samples with European ancestry demonstrated a significant association of this SNP with MDD susceptibility in Val/Val + Val/Met vs. Met/Met (OR =1.231, 95 % CI = 1.046, 1.449; P = 0.013) and Val/Met vs. Met/Met (OR =1.284, 95 % CI = 1.050, 1.484; P = 0.012). For the samples with East Asian ancestry, we found a significant association in both allelic (Val vs. Met: OR =0.835; 95 % CI = 0.714, 0.975; P = 0.023) and genotypic (Met/Met + Val/Met vs. Val/Val: OR =1.431, 95 % CI = 1.143, 1.791; P = 0.002; Val/Met vs. Val/Val: OR =1.482, 95 % CI = 1.171, 1.871; P = 0.001) analyses. No evidence of heterogeneity among studies or publication bias was observed. Together, our results indicate that the COMT Val158Met polymorphism is a vulnerability factor for MDD with distinct effects in different ethnic populations.

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Section: Introductionmentioning

confidence: 99%

Meta-Analysis of the COMT Val158Met Polymorphism in Major Depressive Disorder: Effect of Ethnicity

Wang

Yuan

et al. 2016

J Neuroimmune Pharmacol

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“…First, there are other polymorphisms in the COMT gene that show interaction effects with Val158Met that were not included in this study, and these should be tested [39,40]. Second, COMT gene polymorphism is associated with several psychologic conditions, such as emotion and mood disorders, bipolar disorder, and sensation seeking [41–43]. Although, the participants in this study reported that they have no obvious psychologic disorders (such as emotion and mood disorders, bipolar disorder, and sensation seeking), the future prevalence of these conditions in this study population cannot be assessed.…”

Section: Discussionmentioning

confidence: 96%

Analysis of the Association between Catechol-O-Methyltransferase Val158Met and Male Sexual Orientation

Hong

et al. 2015

The Journal of Sexual Medicine

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Introduction Male sexual orientation is thought to have a genetic component. However, previous studies have failed to generate positive results from among candidate genes. Catechol-O-methyltransferase (COMT), located on chromosome 22, has six exons, spans 27 kb, and encodes a protein of 271 amino acids. COMT has an important role in regulating the embryonic levels of catecholamine neurotransmitters (such as dopamine, norepinephrine, and epinephrine) and estrogens. COMT is also thought to be related to sexual orientation. Aims This study aimed to investigate the relationship between the COMT Val158Met variant and male sexual orientation. We performed association analysis of the COMT gene single nucleotide polymorphism, Val158Met, in 409 homosexual cases and 387 heterosexual control Chinese men. COMT polymorphism status was determined using a polymerase chain reaction-based assay. Methods Polymerase chain reaction was performed to genotype the COMT Val158Met polymorphism. Main Outcome Measures The frequency differences of the genotype and alleles distribution between the male homosexual and control groups. Results Significant differences, both in genotype and alleles, between male homosexual individuals and controls indicated a genetic component related to male homosexuality. The Val allele recessive model could be an interrelated genetic model of the cause of male homosexuality. Conclusion The COMT Val158Met variant might be associated with male sexual orientation and a recessive model was suggested.

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“…POMC gene could be a valuable marker for assessing the response to antidepressant treatment (Chang et al 2015). Furthermore, the polymorphisms of COMT gene are associated with sporadic schizophrenia and mood disorder, respectively (Li et al 2015; Pandolfo et al 2015). COMT inhibitors had been used to ameliorate symptoms of parkinson’s disease (Müller 2015).…”

Section: Discussionmentioning

confidence: 99%

A new bioinformatic insight into the associated proteins in psychiatric disorders

et al. 2016

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BackgroundPsychiatric diseases severely affect the quality of patients’ lives and bring huge economic pressure to their families. Also, the great phenotypic variability among these patients makes it difficult to investigate the pathogenesis. Nowadays, bioinformatics is hopeful to be used as an effective tool for the diagnosis of psychiatric disorders, which can identify sensitive biomarkers and explore associated signaling pathways.MethodsIn this study, we performed an integrated bioinformatic analysis on 1945 mental-associated proteins including 91 secreted proteins and 593 membrane proteins, which were screened from the Universal Protein Resource (Uniport) database. Then the function and pathway enrichment analyses, ontological classification, and constructed PPI network were executed.ResultsOur present study revealed that the majority of mental proteins were closely related to metabolic processes and cellular processes. We also identified some significant molecular biomarkers in the progression of mental disorders, such as HRAS, ALS2, SLC6A1, SLC39A12, SIL1, IDUA, NEPH2 and XPO1. Furthermore, it was found that hub proteins, such as COMT, POMC, NPS and BDNF, might be the potential targets for mental disorders therapy. Finally, we demonstrated that psychiatric disorders may share the same signaling pathways with cancers, involving ESR1, BCL2 and MAPK3.ConclusionOur data are expected to contribute to explaining the possible mechanisms of psychiatric diseases and providing a useful reference for the diagnosis and therapy of them.

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Association of the COMT synonymous polymorphism Leu136Leu and missense variant Val158Met with mood disorders

Cited by 8 publications

References 36 publications

Meta-Analysis of the COMT Val158Met Polymorphism in Major Depressive Disorder: Effect of Ethnicity

Meta-Analysis of the COMT Val158Met Polymorphism in Major Depressive Disorder: Effect of Ethnicity

Analysis of the Association between Catechol-O-Methyltransferase Val158Met and Male Sexual Orientation

A new bioinformatic insight into the associated proteins in psychiatric disorders

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