Association analyses of the DAOA/G30 and D-amino-acid oxidase genes in schizophrenia: Further evidence for a role in schizophrenia
Articolo
Data di Pubblicazione:
2007
Citazione:
Association analyses of the DAOA/G30 and D-amino-acid oxidase genes in
schizophrenia: Further evidence for a role in schizophrenia / T. Shinkai, V. De Luca, R. Hwang, D.J. Muller, M. Lanktree, G. Zai, S. Shaikh, G. Wong, T.R. Sicard, N. Potapova, J. Trakalo, N. King, C. Matsumoto, H. Hori, A.H.C. Wong, O. Ohmori, F. Macciardi, J. Nakamura, J.L. Kennedy. - In: NEUROMOLECULAR MEDICINE. - ISSN 1535-1084. - 9:2(2007), pp. 169-177. [10.1385/NMM:9:2:169]
Abstract:
A number of linkage studies have previously implicated the region of
chromosome 13q34 in schizophrenia. Chumakov and colleagues (2002)
identified a gene complex called G72 (now termed D-amino acid oxidase
activator: DAOA)/G30 in this region and performed association analyses
of the DAOA/G30 as well as the D-amino-acid oxidase (DAAO) gene with
schizophrenia. DAAO oxidizes D-serine, a potent activator of the
N-methyl-D-aspartate (NMDA) type glutamate receptor in the human brain
whereas the DAOA protein is considered an activator of DAAO. The
interaction of these two genes has thus been implicated in the NMDA
receptor regulation pathway in schizophrenia. To date, several studies
have shown a relatively consistent positive association between
schizophrenia and DAOA/G30, but not with DAAO. The aim of our study was
to further evaluate the contributions of these genes to the
susceptibility to schizophrenia using two different sample sets. Our
sample consisted of 168 matched case-control pairs as well as a
family-based sample (n = 113) for transmission disequilibrium test.
Significant associations between the DAOA/G30 M-7 and M-18 polymorphisms
and schizophrenia were observed in our case-control sample whereas no
associations were observed for DAAO markers. We also observed
significant or suggestive transmission disequilibrium for DAOA/G30 M-7,
M-23, and M-24 to probands with schizophrenia in our family-based
sample. Subsequent analysis of haplotypes made up of four DAOA/G30
markers, one marker selected from each of two linkage disequilibrium
blocks that were observed in our sample as well as both ends (M-7 and
M-25), were also associated with schizophrenia. Our data provide further
evidence that the DAOA/G30 locus may play a role in the pathophysiology
of schizophrenia. Although no direct link to genetic polymorphism in
these genes and NMDA receptor function has been revealed, the present
findings support previous reports implicating DAOA/G30 as susceptibility
genes for schizophrenia. Further research is warranted to determine the
functional variation underlying these findings and to relate this to the
pathophysiology of schizophrenia.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Association study; Chromosome 12; Chromosome 13; D-amino-acid oxidase; DAOA; G30; G72; Genetics; Polymorphism; Schizophrenia; Transmission disequilibrium test
Elenco autori:
T. Shinkai, V. De Luca, R. Hwang, D.J. Muller, M. Lanktree, G. Zai, S. Shaikh, G. Wong, T.R. Sicard, N. Potapova, J. Trakalo, N. King, C. Matsumoto, H. Hori, A.H.C. Wong, O. Ohmori, F. Macciardi, J. Nakamura, J.L. Kennedy
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