Synergistic association of mitochondrial uncoupling protein (UCP) genes with schizophrenia

K. Yasuno; S. Ando; S. Misumi; S. Makino; J.K. Kulski; T. Muratake; N. Kaneko; H. Amagane; T. Someya; H. Inoko; H. Suga; K. Kanemoto; G. Tamiya

doi:10.1002/ajmg.b.30443

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Synergistic association of mitochondrial uncoupling protein (UCP) genes with schizophrenia

Journal article

Peer reviewed

Synergistic association of mitochondrial uncoupling protein (UCP) genes with schizophrenia

K. Yasuno, S. Ando, S. Misumi, S. Makino, J.K. Kulski, T. Muratake, N. Kaneko, H. Amagane, T. Someya, H. Inoko, …

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Vol.144B(2), pp.250-253

05/03/2007

DOI: https://doi.org/10.1002/ajmg.b.30443

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Abstract

Many studies suggest that mitochondrial dysfunction is involved in the pathophysiology of schizophrenia. We performed a case-control study using tag SNPs in the mitochondrial uncoupling protein genes, UCP2, UCP4, and BMCP1/UCP5, to investigate their association with schizophrenia. These neuronal UCPs are expressed in various hrain tissues and may exert a neuroprotective effect against increased oxidative stress. We found modest associations between schizophrenia and the four tag SNPs, rs660339 (odds ratio (OR) = 1.330; F = 0.0043) and rs649446 (OR = 0.739; F = 0.0069) in UCP2, and rs10807344 (OR = 0.622; F = 0.0029) and rs2270450 (OR = 0.704; F = 0.0043) in UCP4, all of which were statistically significant even after correcting for multiple comparisons. Moreover, we found a statistically significant synergistic interaction between UCP2 and UCP4 by using the multifactor dimensionality reduction (MDR) method. The synergistic interaction was also confirmed by the logistic regression analysis, where the maximal OR was obtained when the risk alleles at rs660339 and rs10807344 were simultaneously homozygous. Individuals possessing homozygous risk alleles at these two loci have a 7.6-fold risk of developing schizophrenia compared with those of minimal OR. Our findings suggest that UCP2 and UCP4 have a modest but important involvement in the genetic etiology of schizophrenia. This is the first report of the association between schizophrenia and neuronal UCPs.

Details

Title: Synergistic association of mitochondrial uncoupling protein (UCP) genes with schizophrenia
Authors/Creators: K. Yasuno (Author/Creator) - Tokai University
S. Ando (Author/Creator) - Tokai University
S. Misumi (Author/Creator) - Tokai University
S. Makino (Author/Creator) - Tokai University
J.K. Kulski (Author/Creator) - Tokai University
T. Muratake (Author/Creator) - Niigata University
N. Kaneko (Author/Creator) - Niigata University
H. Amagane (Author/Creator) - Niigata University
T. Someya (Author/Creator) - Niigata University
H. Inoko (Author/Creator) - Tokai University
H. Suga (Author/Creator) - Aichi Medical University
K. Kanemoto (Author/Creator) - Aichi Medical University
G. Tamiya (Author/Creator) - National Institute of Advanced Industrial Science and Technology
Publication Details: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Vol.144B(2), pp.250-253
Publisher: Wiley-Liss Inc.
Identifiers: 991005543011007891
Copyright: © 2006 Wiley-Liss, Inc.
Murdoch Affiliation: School of Information Technology
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.26 Diabetes; 1.26.1419 Brown Adipose Tissue
Web Of Science research areas: Genetics & Heredity; Psychiatry
ESI research areas: Molecular Biology & Genetics