NDLI: Epistasis between the DAT 3′ UTR VNTR and the COMT Val158Met SNP on cortical function in healthy subjects and patients with schizophrenia

Content Provider	PubMed Central
Author	Prata, Diana P. Andrea, Mechelli Fu, Cynthia H. Y. Marco, Picchioni Toulopoulou, Timothea Bramon, Elvira Walshe, Muriel Murray, Robin M. Collier, David A. Mcguire, Philip
Abstract	Dopamine has a crucial role in the modulation of neurocognitive function, and synaptic dopamine activity is normally regulated by the dopamine transporter (DAT) and catechol-O-methyltransferase (COMT). Perturbed dopamine function is a key pathophysiological feature of schizophrenia. Our objectives were (i) to examine epistasis between the DAT 3′ UTR variable number of tandem repeats (VNTR) and COMT Val158Met polymorphisms on brain activation during executive function, and (ii) to then determine the extent to which such interaction is altered in schizophrenia. Regional brain response was measured by using blood-oxygen-level-dependent fMRI during an overt verbal fluency task in 85 subjects (44 healthy volunteers and 41 patients with DSM-IV schizophrenia), and inferences were estimated by using an ANOVA in SPM5. There was a significant COMT × DAT nonadditive interaction effect on activation in the left supramarginal gyrus, irrespective of diagnostic group (Z-score = 4.3; family-wise error (FWE) p = 0.03), and in healthy volunteers alone (Z-score = 4.7; FWEp = 0.006). In this region, relatively increased activation was detected only when COMT Met-158/Met-158 subjects also carried the 9-repeat DAT allele, or when, reversely, Val-158/Val-158 subjects carried the 10/10-repeat genotype. Also, there was a significant diagnosis × COMT × DAT nonadditive interaction in the right orbital gyrus (Z-score = 4.3; FWEp = 0.04), where, only within patients, greater activation was only associated with a 9-repeat allele and Val-158 conjunction, and with a 10-repeat and Met-158 conjunction (Z-score = 4.3; FWE p = 0.04). These data demonstrate that COMT and DAT genes interact nonadditively to modulate cortical function during executive processing, and also, that this effect is significantly altered in schizophrenia, which may reflect abnormal dopamine function in the disorder.
Related Links	http://dx.doi.org/10.1073/pnas.0903007106
Starting Page	13600
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	32
Volume Number	106
Language	English
Publisher	National Academy of Sciences
Publisher Date	2009-08-11
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission

Catechol-o-methyl transferase (COMT) val158met polymorphism and adolescent cortical development in patients with childhood-onset schizophrenia, their non-psychotic siblings, and healthy controls

Differential Effects of the Catechol-O-Methyltransferase Val158Met Genotype on the Cognitive Function of Schizophrenia Patients and Healthy Japanese Individuals

Association between the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism and Manual Aiming Control in Healthy Subjects

No association between Val158Met of the COMT gene and susceptibility to schizophrenia in the Syrian population

Association study of the functional Catechol-O-Methyltranferase (COMT) Val158Met polymorphism on executive cognitive function in a Thai sample

Association between the Catechol O-Methyltransferase (COMT) Val158met Polymorphism and Different Dimensions of Impulsivity

The influence of COMT Val158Met genotype on the character dimension cooperativeness in healthy females

Association between the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism and Alexithymia in Patients with Obsessive-Compulsive Disorder

Epistasis between the DAT 3′ UTR VNTR and the COMT Val158Met SNP on cortical function in healthy subjects and patients with schizophrenia

Similar Documents

Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission

Catechol-o-methyl transferase (COMT) val158met polymorphism and adolescent cortical development in patients with childhood-onset schizophrenia, their non-psychotic siblings, and healthy controls

Differential Effects of the Catechol-O-Methyltransferase Val158Met Genotype on the Cognitive Function of Schizophrenia Patients and Healthy Japanese Individuals

Association between the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism and Manual Aiming Control in Healthy Subjects

No association between Val158Met of the COMT gene and susceptibility to schizophrenia in the Syrian population

Association study of the functional Catechol-O-Methyltranferase (COMT) Val158Met polymorphism on executive cognitive function in a Thai sample

Association between the Catechol O-Methyltransferase (COMT) Val158met Polymorphism and Different Dimensions of Impulsivity

The influence of COMT Val158Met genotype on the character dimension cooperativeness in healthy females

Association between the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism and Alexithymia in Patients with Obsessive-Compulsive Disorder

Epistasis between the DAT 3′ UTR VNTR and the COMT Val158Met SNP on cortical function in healthy subjects and patients with schizophrenia