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Genetic Variations of DAOA (rs947267 and rs3918342) and COMT Genes (rs165599 and rs4680) in Schizophrenia and Bipolar I Disorder.

ABSTRACT: Introduction:Genetic and environmental factors are involved in the incidence of schizophrenia and bipolar disorder. Many reports confirm that several common genes are connected with these two psychotic disorders. Several neurotransmitters may be involved in the molecular mechanisms of schizophrenia and bipolar disorder. We aimed to estimate the role of two talent genes: DAOA in neurotransmission of glutamate and COMT in neurotransmission of dopamine to guide the treatment of schizophrenia and bipolar disorder. Methods:Blood samples (n=100 for schizophrenia, n=100 for bipolar I disorder and n=127 for case control) were collected from individuals unrelated in the southwest of Iran. The SNPs (rs947267 and rs3918342 for DAOA gene/rs165599 and rs4680 for COMT gene) were genotyped using the PCR-RFLP method. Our finding was studied by logistic regression and Mantel-Haenszel Chi-square tests. Results:We observed an association in rs3918342, rs165599 and rs4680 single nucleotide polymorphisms and schizophrenia and bipolar I disorder. In addition, our data demonstrated that the rs947267 was related to bipolar I disorder but there was no association between this SNP and schizophrenia. Conclusion:In conclusion, this result supports the hypothesis that variations in DAOA and COMT genes may play a role in schizophrenia and bipolar disorder.

SUBMITTER: Ahmadi L

PROVIDER: S-EPMC6359688 | biostudies-literature | 2018 Nov-Dec

REPOSITORIES: biostudies-literature

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Genetic Variations of <i>DAOA</i> (rs947267 and rs3918342) and <i>COMT</i> Genes (rs165599 and rs4680) in Schizophrenia and Bipolar I Disorder.

Ahmadi Leila L Kazemi Nezhad Seyed Reza SR Behbahani Parisima P Khajeddin Nilofar N Pourmehdi-Boroujeni Mehdi M

Basic and clinical neuroscience 20181101 6

<h4>Introduction</h4>Genetic and environmental factors are involved in the incidence of schizophrenia and bipolar disorder. Many reports confirm that several common genes are connected with these two psychotic disorders. Several neurotransmitters may be involved in the molecular mechanisms of schizophrenia and bipolar disorder. We aimed to estimate the role of two talent genes: <i>DAOA</i> in neurotransmission of glutamate and <i>COMT</i> in neurotransmission of dopamine to guide the treatment o ...[more]

PMID: 30719257

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Project description:IntroductionBipolar disorder is characterized by severe mood symptoms including major depressive and manic episodes. During manic episodes, many patients show cognitive dysfunction. Dopamine and glutamate are important for cognitive processing, thus the COMT and DAOA genes that modulate the expression of these neurotransmitters are of interest for studies of cognitive function.MethodologyFocusing on the most severe episode of mania, a factor was found with the combined symptoms of talkativeness, distractibility, and thought disorder, considered a cognitive manic symptoms (CMS) factor. 488 patients were genotyped, out of which 373 (76%) had talkativeness, 269 (55%) distractibility, and 372 (76%) thought disorder. 215 (44%) patients were positive for all three symptoms, thus showing CMS (Table 1). As population controls, 1,044 anonymous blood donors (ABD) were used. Case-case and case-control design models were used to investigate genetic associations between cognitive manic symptoms in bipolar 1 disorder and SNPs in the COMT and DAOA genes. [Table: see text].ResultsThe finding of this study was that cognitive manic symptoms in patients with bipolar 1 disorder was associated with genetic variants in the DAOA and COMT genes. Nominal association for DAOA SNPs and COMT SNPs to cognitive symptoms factor in bipolar 1 disorder was found in both allelic (Table 2) and haplotypic (Table 3) analyses. Genotypic association analyses also supported our findings. However, only one association, when CMS patients were compared to ABD controls, survived correction for multiple testing by max (T) permutation. Data also suggested interaction between SNPs rs2391191 in DAOA and rs5993883 in COMT in the case-control model. [Table: see text] [Table: see text].ConclusionIdentifying genes associated with cognitive functioning has clinical implications for assessment of prognosis and progression. Our finding are consistent with other studies showing genetic associations between the COMT and DAOA genes and impaired cognition both in psychiatric disorders and in the general population.

Project description:Impulsivity has been proposed as an endophenotype for bipolar disorder (BD); moreover, impulsivity levels have been shown to carry prognostic significance and to be quality-of-life predictors. To date, reports about the genetic determinants of impulsivity in mood disorders are limited, with no studies on BD individuals. Individuals with BD and healthy controls (HC) were recruited in the context of an observational, multisite study (GECOBIP). Subjects were genotyped for three candidate single-nucleotide polymorphisms (SNPs) (5-HTTLPR, COMT rs4680, BDNF rs6265); impulsivity was measured through the Italian version of the Barratt Impulsiveness Scale (BIS-11). A mixed-effects regression model was built, with BIS scores as dependent variables, genotypes of the three polymorphisms as fixed effects, and centers of enrollment as random effect. Compared to HC, scores for all BIS factors were higher among subjects with euthymic BD (adjusted β for Total BIS score: 5.35, p < 0.001). No significant interaction effect was evident between disease status (HC vs. BD) and SNP status for any polymorphism. Considering the whole sample, BDNF Met/Met homozygosis was associated with lower BIS scores across all three factors (adjusted β for Total BIS score: −10.2, p < 0.001). A significant 5-HTTLPR x gender interaction was found for the SS genotype, associated with higher BIS scores in females only (adjusted β for Total BIS score: 12.0, p = 0.001). Finally, COMT polymorphism status was not significantly associated with BIS scores. In conclusion, BD diagnosis did not influence the effect on impulsivity scores for any of the three SNPs considered. Only one SNP—the BDNF rs6265 Met/Met homozygosis—was independently associated with lower impulsivity scores. The 5-HTTLPR SS genotype was associated with higher impulsivity scores in females only. Further studies adopting genome-wide screening in larger samples are needed to define the genetic basis of impulsivity in BD.

Project description:Schizophrenia and bipolar disorder may share aspects of genetic etiology. Evidence supports the Val 108/158 Met polymorphism of the Catechol-o-Methyltransferase (COMT) gene as potentially contributing to the etiology of both disorders. To determine whether the COMT gene is associated with personality traits related to genetic risk for either schizophrenia or bipolar disorder, we examined dimensions of personality psychopathology in biological relatives of individuals with the disorders. Specifically, we contrasted personality characteristics of first-degree relatives of people with schizophrenia, first-degree relatives of people with bipolar-I disorder, and nonpsychiatric control participants using scores from the Dimensional Assessment of Personality Pathology-Brief Questionnaire (DAPP-BQ). We also characterized the COMT Val 108/158 Met polymorphism of subjects. Compared to controls, relatives of schizophrenia patients scored lower on stimulus seeking and higher on restrictive expression and social avoidance. Compared to relatives of bipolar patients, relatives of schizophrenia patients had lower scores on narcissism, rejectionality (i.e., rejection of ideas of others), stimulus seeking, passive-aggressive oppositionality, and self-harm. The subset of relatives of schizophrenia patients who were COMT val homozygotes exhibited lower scores on narcissism, rejectionality, and stimulus seeking than met homozygote relatives of schizophrenia patients and control participants. Although relatives of bipolar patients showed scale elevations consistent with emotional dysregulation, the scores failed to be associated with the Val 108/158 Met polymorphism. Abnormally low narcissism and rejectionality in val homozygote relatives of schizophrenia patients suggests that the val allele of the COMT polymorphism may be associated with an underdeveloped self-concept phenomenologically similar to made volition and passivity experiences comprising first-rank symptoms of schizophrenia.

Dataset Information

Genetic Variations of DAOA (rs947267 and rs3918342) and COMT Genes (rs165599 and rs4680) in Schizophrenia and Bipolar I Disorder.

Publications

Genetic Variations of <i>DAOA</i> (rs947267 and rs3918342) and <i>COMT</i> Genes (rs165599 and rs4680) in Schizophrenia and Bipolar I Disorder.

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