Epigenetic modifications of the membrane bound catechol-O-methyltransferase (MB-COMT) gene may affect the enzymatic degradation of dopamine, and consequently, human behavior. This study investigated the association between membrane bound catechol-O-methyltransferase DNA methylation (DNAm) differences in 92 monozygotic (MZ) twins with phenotypic manifestations of cognitive, behavioral, and personality indicators associated with reward-related behaviors and lack of control. We used pyrosequencing to determine DNAm of the regulatory region of membrane bound catechol-O-methyltransferase in saliva DNA. Results of intrapair differences in the percentage of membrane bound catechol-O-methyltransferase DNAm at each of five CpG sites show that there are associations between phenotypic indicators of lack of control and membrane bound catechol-O-methyltransferase DNAm differences on CpG1, CpG2 and CpG4, suggesting the common epigenetic patterns for personality traits, cognitive functions, and risk behaviors.

/pdf/differences-in-mb-comt-dna-methylation-in-monozygotic-twins-2onkbup9.pdf

Differences in MB-COMT DNA methylation in monozygotic twins on phenotypic indicators of impulsivity

Purpose of the study. To determine clinical, morphometric, genetic predictors of non-refractory and refractory variants of the course of irritable bowel syndrome (IBS).Materials and methods. We examined 148 patients with non-refractory (41 people) and refractory (107 people) the course of irritable bowel syndrome. The control group consisted of 36 healthy volunteers. The analysis of the symptoms of the current exacerbation of the disease, veriﬁ cation of comorbid gastroenterological pathology (taking into account the Roman criteria- IV and Russian recommendations), assessment of signs of psychological maladaptation (The Four-D imensional Symptom Questionnaire), ﬁ brocolonoscopy, immunohistochemical, morphometric study of colobiopts, determination of the expression area of colonocytes immunopositive to motilin and sirtuin-1, determination of genotypes of polymorphic marker rs4680 of the СOMT gene by polymerase chain reaction.Results. The intensity of abdominal pain, the severity of “intestinal” symptoms was higher in refractory IBS compared with non-refractory. Functional comorbidity (functional dyspepsia, functional disorder of the gallbladder) was more common in the refractory variant of the course of the disease, mainly with diarrhea. Indicators of distress, depression, anxiety, somatization in the refractory course of the disease were higher compared to non-refractory, did not diﬀ er signiﬁ cantly in IBS with constipation and diarrhea. The indicators of the expression area of motilin-p ositive colonocytes were reduced in IBS with constipation, increased in IBS with diarrhea (the maximum changes were in the refractory variant of the course of the disease). The expression area of sirtuin-1-positive colonocytes was reduced in IBS with diarrhea compared to IBS with constipation and with the control group. Associations of genotypes of the polymorphic marker rs4680 of the СOMT gene with a refractory variant of the course of IBS, as well as with the severity of abdominal pain syndrome and signs of psychological maladaptation were found.Conclusion. Patients with irritable bowel syndrome are characterized by functional comorbidity, signs of psychological maladaptation, more pronounced in the refractory variant of the course of the disease. Patients with IBS, in comparison with the control group, are characterized by a change in the expression area of motilin- and sirtuin-1-positive colonocytes, correlating with the variant of intestinal dysfunction and maximally expressed in the refractory course of the disease. Variants of the course of irritable bowel syndrome are associated with polymorphic markers rs4680 of the gene of the enzyme СOMT.

Irritable bowel syndrome: extra- intestinal comorbidity, psychological, morphometric and genetic predictors of variants of the course of the disease

Numerous studies have established associations between single nucleotide polymorphisms (SNPs) and various behavioral and neurodevelopmental conditions. This study explores the links between SNPs in candidate genes involved in central nervous system (CNS) physiology and their implications for the behavioral and emotional aspects in children and teenagers. A total of 590 participants, aged 7-15 years, from the Early Life Exposures In Mexico To Environmental Toxicants (ELEMENT) cohort study in Mexico City, underwent genotyping for at least one of 15 CNS gene-related SNPs at different timepoints. We employed multiple linear regression models to assess the potential impact of genetic variations on behavioral and cognitive traits, as measured by the Behavioral Assessment System for Children (BASC) and Conners parent rating scales. Significant associations were observed, including the rs1800497 TC genotype (ANKK1) with the Cognitive Problems/Inattention variable (p value = 0.003), the rs1800955 CT genotype (DDR4) with the Emotional Lability Global index variable (p value = 0.01), and the rs10492138 GA and rs7970177 TC genotypes (GRIN2B) with the Depression variable (p values 0.007 and 0.012, respectively). These finds suggest potential genetic profiles associated with "risk" and "protective" behaviors for these SNPs. Our results provide valuable insights into the role of genetic variations in neurobehavior and highlight the need for further research in the early identification and intervention in individuals at risk for these conditions. 

Single nucleotide polymorphisms of ANKK1, DDR4, and GRIN2B genes predict behavior in a prospective cohort of Mexican children and adolescents

The aim of the study was to explore the possible vulnerability (diathesis-stress), susceptibility (differential susceptibility), or vantage (vantage sensitivity) properties of COMT gen Val158Met polymorphism to adverse and favorable parenting styles from both parents in relation to children’s reactive and proactive aggressive behavior. Within 279 eight-year-old children (125 girls and 154 boys) from Spain, reactive and proactive aggressive behavior was measured through the “Reactive and Proactive Questionnaire” (RPQ). Saliva samples were collected to genotype for the COMT Val158Met polymorphism via real-time PCR. Finally, parenting styles were assessed using the “Parenting Styles and Dimensions Questionnaire” (PSDQ). The results revealed that for boys, the Met allele was a vulnerability factor for proactive aggression in response to low-authoritative parenting from the father. For girls, it was the Val allele, the vulnerability variable to the high authoritarian style of the father, and the susceptibility factor to the authoritative style of the mother over proactive aggression. The results are discussed, considering possible sex differences. Our results indicate that the COMT Val158Met polymorphism is a biological variable that confers greater sensitivity to the environment.

The Val158Met Polymorphism in 8-Year-Old Boys and Girls Moderates the Influence of Parenting Styles on Proactive Aggression: Testing the Sensitivity to the Environment

Childhood trauma is a serious form of stress that makes individuals more vulnerable to developing Schizophrenia (SCZ). Many studies have predicted the association between the catechol-O-methyltransferase (COMT) gene Val158Met variant and aggressive attack. We aimed to investigate the association the COMT variant and childhood trauma on aggression in Turkish SCZ patientsThis study included 89 patients diagnosed with SCZ. Childhood Trauma Questionnaire (CTS) and Overt Aggression Scale (OAS) were used to assess childhood trauma and aggression. COMT Val158Met variant was analyzed by PCR-RFLP method from isolated DNAs.There was no statistically significant difference in comparing the COMT genotype distribution and clinical characteristics including suicide attempts, self-destructive behavior, crime history, substance, alcohol and tobacco use. When we evaluate Spearman's rank correlation coefficients between CTQ and OAS, the correlation between the OAS and CTQ scores of the patients was statistically significant except for the sexual abuse subgroup of the CTQ. In the univariate logistic regression analysis, in which the dichotomized OAS score was accepted as the dependent variable, it was found that age, suicide attempt, substance abuse, and CTQ total score significantly predicted the higher OAS scores. In the multivariate logistic regression analysis, which included the variables that predicted OAS significantly, age, suicide attempt, and total CTQ score were determined as independent variables predicting OAS.Because of the phenotypic complexity in SCZ, it is difficult to draw strong conclusions about COMT and to highlight a definitive relationship. Larger-scale studies are needed to examine the multifactorial inheritance pattern of schizophrenia in different dimensions.

Evaluation of the association COMT Val158Met variant and childhood trauma on aggression in Turkish SCZ patients.

Accumulating research has identified the interactive effects of catechol-O-methyltransferase (COMT) gene Val158Met polymorphism and environmental factors on aggression. However, available evidence was mainly based upon correlational design, which yields mixed findings concerning who (Val vs. Met carriers) are more affected by environmental conditions and has been challenged for the low power of analyses on gene-environment interaction. Drawing on a mixed design, we scrutinized how COMT Val158Met polymorphism (between-group variable) impacts on aggression, assessed by hostility, aggressive motivation, and aggressive behavior, under different social conditions (exclusion vs. inclusion, within-group variable) in a sample of 70 Chinese male undergraduate students. We found that both Val/Val homozygote and Met alleles carriers showed differences in the feelings of hostility and aggressive motivation under conditions of exclusion versus inclusion, but these differences were more pronounced for Met allele carriers. These findings implied that COMT Val158Met polymorphism did not respond to environmental stimuli in an all-or-none way and shed light on the importance of examining the gene-environment interaction using a mixed design.

/pdf/catechol-o-methyltransferase-gene-val158met-polymorphism-3gb54fmrs2.pdf

Catechol-O-Methyltransferase Gene Val158Met Polymorphism Moderates the Effect of Social Exclusion and Inclusion on Aggression in Men: Findings From a Mixed Experimental Design

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Catechol-O-Methyltransferase Gene Val158Met Polymorphism Moderates the Effect of Social Exclusion and Inclusion on Aggression in Men: Findings From a Mixed Experimental Design