Association of the gene encoding neurogranin with schizophrenia in males.
The neurogranin (NRGN) gene produces a postsynaptic brain-specific protein that regulates calmodulin-Ca(2+) availability in neurons. Acting downstream of the NMDA receptor and upstream of calcineurin and other proteins implicated in schizophrenia, NRGN is a good candidate for association studies in schizophrenia. NRGN expression is regulated during development and is modulated by thyroid hormones and retinoids, molecules essential for the proper development of the central nervous system. Given the genetic complexity of schizophrenia and the potential genetic heterogeneity in different populations, we studied a possible association of NRGN with schizophrenia in 73 Azorean proband-parent triads and in two independent case-control samples from the Portuguese-mainland (244 schizophrenic and 210 controls) and Brazil (69 schizophrenic and 85 mentally healthy individuals). Genotype distribution showed association of the rs7113041 SNP with schizophrenia in males of Portuguese origin, which was confirmed by the analysis of the proband-parent triads. This evidence, implicating NRGN in schizophrenia, introduces another player into the glutamatergic hypothesis of schizophrenia.
Ruano
Dina
D
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.
Aulchenko
Yurii S
YS
Macedo
António
A
Soares
Maria J
MJ
Valente
José
J
Azevedo
Maria H
MH
Hutz
Mara H
MH
Gama
Clarissa S
CS
Lobato
Maria I
MI
Belmonte-de-Abreu
Paulo
P
Goodman
Ann B
AB
Pato
Carlos
C
Heutink
Peter
P
Palha
Joana A
JA
D017668:Age of Onset; D001394:Azores; D001938:Brazil; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D005788:Gene Pool; D006580:Genetic Carrier Screening; D005819:Genetic Markers / Q000235:genetics; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D051579:Neurogranin / Q000235:genetics*; D009711:Nucleotides / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011174:Portugal; D012559:Schizophrenia / Q000235:genetics*
D005819:Genetic Markers; D009711:Nucleotides; D051579:Neurogranin