Effect of metabotropic glutamate receptor 3 genotype on N-acetylaspartate measures in the dorsolateral prefrontal cortex.
OBJECTIVE
This study was carried out to confirm prior evidence of an effect of a single nucleotide polymorphism (SNP) in the metabotropic glutamate receptor 3 (GRM3) gene (a putative risk factor for schizophrenia) on measures of N-acetylaspartate in healthy comparison subjects.


METHODS
Fifty-four carefully screened healthy volunteers genotyped at SNP rs6465084 underwent magnetic resonance spectroscopic imaging (MRSI) at 3 T and selected neuropsychological testing.


RESULTS
The A/A genotype group exhibited a significant reduction of N-acetylaspartate/creatine levels in the right dorsolateral prefrontal cortex compared to the G carriers. A tendency in the same direction was seen in the left dorsolateral prefrontal cortex and in the white matter adjacent to the prefrontal cortex.


CONCLUSIONS
These findings provide further evidence that GRM3 affects prefrontal function and that variation in GRM3, monitored by SNP rs6465084, affects GRM3 function.
Genes and Cognition Program, Clinical Brain Disorders Branch, Intramural Research Program, Bldg. 10, Rm. 4S235, 10 Center Dr., NIMH, NIH, Bethesda, MD 20892, USA. marencos@mail.nih.gov
Stefano
S
Marenco
Sonya U
SU
Steele
Michael F
MF
Egan
Terry E
TE
Goldberg
Richard E
RE
Straub
Anjail Z
AZ
Sharrief
Daniel R
DR
Weinberger
D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D003401:Creatine / Q000032:analysis; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007438:Introns / Q000235:genetics / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000502:physiology; D017397:Prefrontal Cortex / Q000737:chemistry* / Q000378:metabolism / Q000503:physiopathology; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology
D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine