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

研究成果: Article査読

33 被引用数 (Scopus)


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.

ジャーナルAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
出版ステータスPublished - 2007 3 5

ASJC Scopus subject areas

  • 遺伝学(臨床)
  • 精神医学および精神衛生
  • 細胞および分子神経科学


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