14-3-3 protein η chain gene (YWHAH) polymorphism and its genetic association with schizophrenia
Kazuhiko Toyooka
National Saigata Hospital, Saigata, Ogata, Japan
Department of Psychiatry, Niigata University School of Medicine, Asahimachi, Niigata, Japan
Search for more papers by this authorCorresponding Author
Tatsuyuki Muratake
National Saigata Hospital, Saigata, Ogata, Japan
Department of Psychiatry, Niigata University School of Medicine, Asahimachi, Niigata, Japan
Department of Psychiatry, Niigata University School of Medicine, Asahimachi, Niigata 951-8510, JapanSearch for more papers by this authorToshihisa Tanaka
Department of Psychiatry, Niigata University School of Medicine, Asahimachi, Niigata, Japan
Search for more papers by this authorShuichi Igarashi
Department of Neurology, Brain Research Institute, Niigata University, Asahimachi, Niigata, Japan
Search for more papers by this authorHiromi Watanabe
National Saigata Hospital, Saigata, Ogata, Japan
Search for more papers by this authorHiromori Takeuchi
National Saigata Hospital, Saigata, Ogata, Japan
Search for more papers by this authorShigenobu Hayashi
National Saigata Hospital, Saigata, Ogata, Japan
Search for more papers by this authorMasaya Maeda
Department of Psychiatry, Niigata University School of Medicine, Asahimachi, Niigata, Japan
Search for more papers by this authorMakoto Takahashi
Department of Psychiatry, Niigata University School of Medicine, Asahimachi, Niigata, Japan
Search for more papers by this authorShoji Tsuji
Department of Neurology, Brain Research Institute, Niigata University, Asahimachi, Niigata, Japan
Search for more papers by this authorToshiro Kumanishi
Department of Molecular Neuropathology, Brain Research Institute, Niigata University, Asahimachi, Niigata, Japan
Search for more papers by this authorYasuo Takahashi
National Saigata Hospital, Saigata, Ogata, Japan
Department of Molecular Neuropathology, Brain Research Institute, Niigata University, Asahimachi, Niigata, Japan
Search for more papers by this authorKazuhiko Toyooka
National Saigata Hospital, Saigata, Ogata, Japan
Department of Psychiatry, Niigata University School of Medicine, Asahimachi, Niigata, Japan
Search for more papers by this authorCorresponding Author
Tatsuyuki Muratake
National Saigata Hospital, Saigata, Ogata, Japan
Department of Psychiatry, Niigata University School of Medicine, Asahimachi, Niigata, Japan
Department of Psychiatry, Niigata University School of Medicine, Asahimachi, Niigata 951-8510, JapanSearch for more papers by this authorToshihisa Tanaka
Department of Psychiatry, Niigata University School of Medicine, Asahimachi, Niigata, Japan
Search for more papers by this authorShuichi Igarashi
Department of Neurology, Brain Research Institute, Niigata University, Asahimachi, Niigata, Japan
Search for more papers by this authorHiromi Watanabe
National Saigata Hospital, Saigata, Ogata, Japan
Search for more papers by this authorHiromori Takeuchi
National Saigata Hospital, Saigata, Ogata, Japan
Search for more papers by this authorShigenobu Hayashi
National Saigata Hospital, Saigata, Ogata, Japan
Search for more papers by this authorMasaya Maeda
Department of Psychiatry, Niigata University School of Medicine, Asahimachi, Niigata, Japan
Search for more papers by this authorMakoto Takahashi
Department of Psychiatry, Niigata University School of Medicine, Asahimachi, Niigata, Japan
Search for more papers by this authorShoji Tsuji
Department of Neurology, Brain Research Institute, Niigata University, Asahimachi, Niigata, Japan
Search for more papers by this authorToshiro Kumanishi
Department of Molecular Neuropathology, Brain Research Institute, Niigata University, Asahimachi, Niigata, Japan
Search for more papers by this authorYasuo Takahashi
National Saigata Hospital, Saigata, Ogata, Japan
Department of Molecular Neuropathology, Brain Research Institute, Niigata University, Asahimachi, Niigata, Japan
Search for more papers by this authorAbstract
Recent genetic analyses have suggested a linkage between schizophrenia and the chromosomal region 22q12–q13. 14-3-3 protein, abundant in the brain, mediates interactions between diverse molecules of biological activities; its gene was recently mapped to chromosome 22q12.1–q13.1. We therefore investigated allele frequencies of a variable number of tandem repeat (VNTR) in the 5′-noncoding region of the 14-3-3 η chain gene in controls and schizophrenics. The frequencies of the two-repeat allele were significantly higher (P < 0.05) in the schizophrenics, and particularly in those with onset before age 22 (early-onset schizophrenics, P < 0.02), than in the controls. The odds ratio was significantly increased in the early-onset schizophrenics homozygous for the two-repeat allele (OR = 3.3, 95% CI = 1.1—9.7). The 14-3-3 η chain gene is a potential susceptibility gene for schizophrenia, and particularly for early-onset schizophrenia. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:164–167, 1999. © 1999 Wiley-Liss, Inc.
REFERENCES
- Aitken A. 1995. 14–3–3 proteins on the MAP. Trends Biochem Sci 20: 95–97.
- Aitken A. 1996. 14–3–3 and its possible role in co-ordinating multiple signalling pathways. Trends Cell Biol 6: 341–347.
- American Psychiatric Association. 1987. Diagnostic and statistical manual of mental disorders, Third Edition, Revised (DSM-III-R). Washington, DC: American Psychiatric Association.
- Barondes SH, Alberts BM, Andreasen NC, Bargmann C, Benes F, Goldman-Rakic, P, Gottesman, I, Heinemann, SF, Jones, EG, Kirschner, M, Lewis, D, Raff, M, Roses, A, Rubenstein, J, Snyder, S, Watson, SJ, Weinberger, DR, Yolken, RH. 1997. Workshop on schizophrenia. Proc Natl Acad Sci USA 94: 1612–1614.
- Carlsson A. 1988. The current status of the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 1: 179–186.
- Coon H, Jensen S, Holik J, Hoff M, Myles-Worsley, M, Reimherr, F, Wender, P, Waldo, M, Freedman, R, Leppert, M, Byerley, W. 1994. Genomic scan for genes predisposing to schizophrenia. Am J Med Genet 54: 59–71.
- Crowe RR. 1993. Candidate genes in psychiatry: An epidemiological perspective. Am J Med Genet 48: 74–77.
-
Gill M,
Vallada H,
Collier D,
Sham P,
Holmans P,
Murray R,
McGuffin P,
Nanko S,
Owen M,
Antonarakis S,
Housman D,
Kazazian H,
Nestadt G,
Pulver AE,
Straub RE,
MacLean CJ,
Walsh D,
Kendler KS,
DeLisi L,
Polymeropoulos M,
Coon H,
Byerley W,
Lofthouse R,
Gershon E,
Golden L,
Crow T,
Byerley W,
Coon H,
Freedman R,
Laurent C,
Bodeau-Pean, S,
d'Amato, T,
Jay, M,
Campion, D,
Mallet, J,
Wildenauer, DB,
Lerer, B,
Albus, M,
Ackenheil, M,
Ebstein, RP,
Hallmayer, J,
Maier, W,
Gurling, H,
Curtis, D,
Kalsi, G,
Brynjolfsson, J,
Sigmundson, T,
Petursson, H,
Blackwood, D,
Muir, W,
St. Clair, D,
He, L,
Maguire, S,
Moises, HW,
Hwu, HG,
Yang, L,
Wiese, C,
Tao, L,
Liu, X,
Kristbjarnason, H,
Levinson, DF,
Mowry, BJ,
Donis-Keller, H,
Hayward, NK,
Crowe, RR,
Silverman, JM,
Nancarrow, DJ,
Read, CM.
1996.
A combined analysis of D22S278 marker alleles in affected sib-pairs: Support for a susceptibility locus for schizophrenia at chromosome 22ql2.
Am J Med Genet
67:
40–45.
10.1002/(SICI)1096-8628(19960216)67:1<40::AID-AJMG6>3.0.CO;2-W PubMed Web of Science® Google Scholar
- Gordon CT, Frazier JA, McKenna K, Giedd J, Zametkin A, Zahn T, Hommer D, Hong W, Kaysen D, Albus KE, Rapoport JL. 1994. Childhood-onset schizophrenia: An NIMH study in progress. Schizophr Bull 20: 697–712.
- Gottesman II. 1992. Schizophrenia genesis: The origins of madness. New York: W.H. Freedman. p 82–149.
- Hollis C. 1995. Child and adolescent (juvenile onset) schizophrenia. A case control study of premorbid developmental impairments. Br J Psychiatry 166: 489–495.
- Ichimura T, Isobe T, Okuyama T, Yamauchi T, Fujisawa H. 1987. Brain 14–3–3 protein is an activator protein that activates tryptophan 5 monooxygenase and tyrosine 3-monooxygenase in the presence of Ca2+, calmodulin-dependent protein kinase II. FEBS Lett 219:79–82.
- Ichimura T, Isobe T, Okuyama T, Takahashi N, Araki K, Kuwano R, Takahashi Y. 1988. Molecular cloning of cDNA coding for brain-specific 14–3–3 protein, a protein kinase-dependent activator of tyrosine and tryptophan hydroxylases. Proc Natl Acad Sci USA 85: 7084–7088.
- Ichimura T, Uchiyama J, Kunihiro O, Ito M, Horigome T, Omata S, Shinkai F, Kaji H, Isobe T. 1995. Identification of the site of interaction of the 14–3–3 protein with phosphorylated tryptophan hydroxylase. J Biol Chem 270: 28515–28518.
- Ichimura-Ohshima, Y, Morii, K, Ichimura, T, Araki, K, Takahashi, Y, Isobe, T, Minoshima, S, Fukuyama, R, Shimizu, N, Kuwano, R. 1992. cDNA cloning and chromosomal assignment of the gene for human brain 14–3–3 protein→ chain. J Neurosci Res 31: 600–605.
- Kidd KK. 1993. Associations of disease with genetic markers: Déjà vu all over again. Am J Med Genet 48: 71–73.
- McGuffin P. 1988. Genetics of schizophrenia. In: P Bebbington, P McGuffin, editors. Schizophrenia, the major issues. London: Heinemann Medical. p 107–126.
- Moises HW, Yang L, Li T, Havsteen B, Fimmers R, Baur MP, Liu X, Gottesman II. 1995. Potential linkage disequilibrium between schizophrenia and locus D22S278 on the long arm of chromosome 22. Am J Med Genet 60: 465–467.
- Muratake T, Hayashi S, Ichikawa T, Kumanishi T, Ichimura Y, Kuwano R, Isobe T, Wang Y, Minoshima S, Shimizu N, Takahashi Y. 1996. Structural organization and chromosomal assignment of the human 14–3–3→ chain gene (YWHAH). Genomics 36: 63–69.
- Pulver AE, Karayiorgou M, Wolyniec PS, Lasseter VK, Kasch L, Nestadt G, Antonarakis S, Housman D, Kazazian HH, Meyers D, Ott J, Lamacz M, Liang KY, Hanfelt J, Ullrich G, DeMarchi N, Ramu E, McHugh PR, Adler L, Thomas M, Carpenter WT, Manschreck T, Gordon CT, Kimberland M, Babb R, Puck J, Childs B. 1994. Sequential strategy to identify a susceptibility gene for schizophrenia: Report of potential linkage on chromosome 22q12—q13.1: Part 1. Am J Med Genet 54: 36–43.
- Skoulakis EMC, Davis RL. 1996. Olfactory learning deficits in mutants for leonardo, a Drosophila gene encoding a 14–3–3 protein. Neuron 17: 931–944.
- Vallada H, Curtis D, Sham PC, Murray RM, McGuffin P, Nanko S, Gill M, Owen M, Collier DA. 1995. Chromosome 22 markers demonstrate transmission disequilibrium with schizophrenia. Psychiatr Genet 5: 127–130.
- Waddington JL. 1993. Schizophrenia: Developmental neuroscience and pathology. Lancet 341: 531–536.
- Watanabe M, Isobe T, Okuyama T, Ichimura T, Kuwano R, Takahashi Y, Kondo H. 1991. Molecular cloning of cDNA to rat 14–3–3→ chain polypeptide and the neuronal expression of the mRNA in the central nervous system. Mol Brain Res 10: 151–158.
- Watanabe M, Isobe T, Ichimura T, Kuwano R, Takahashi Y, Kondo H. 1993. Developmental regulation of neuronal expression for the→ subtype of the 14–3–3 protein, a putative regulatory protein for protein kinase C. Dev Brain Res 73: 225–235.
- Woolf B. 1955. On estimating the relation between blood group and disease. Ann Hum Genet 19: 251–253.
- Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ. 1996. Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14–3–3 not to BCL-XL. Cell 87: 619–628.
