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

Katsuhito Yasuno, Satoshi Ando, Shinnosuke Misumi, Satoshi Makino, Jerzy K. Kulski, Tatsuyuki Muratake, Naoshi Kaneko, Hideki Amagane, Toshiyuki Someya, Hidetoshi Inoko, Hidemichi Suga, Kousuke Kanemoto, Gen Tamiya

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31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)250-253
Number of pages4
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume144
Issue number2
DOIs
Publication statusPublished - 2007 Mar 5
Externally publishedYes

Keywords

  • Association study
  • Schizophrenia
  • Synergistic interaction
  • Tag SNP
  • Uncoupling protein

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Yasuno, K., Ando, S., Misumi, S., Makino, S., Kulski, J. K., Muratake, T., Kaneko, N., Amagane, H., Someya, T., Inoko, H., Suga, H., Kanemoto, K., & Tamiya, G. (2007). Synergistic association of mitochondrial uncoupling protein (UCP) genes with schizophrenia. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 144(2), 250-253. https://doi.org/10.1002/ajmg.b.30443