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Association of TOMM40 Polymorphisms with Late-Onset Alzheimer’s Disease in a Northern Han Chinese Population

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Abstract

Mitochondrial dysfunction is an early defect in the pathogenesis of late-onset Alzheimer’s disease (LOAD). One interesting candidate gene for mitochondrial dysfunction in LOAD is the translocase of outer mitochondrial membrane 40 homolog (TOMM40) gene. Several single nucleotide polymorphisms (SNPs) within TOMM40 have been shown to affect susceptibility to LOAD in Caucasians, while there are no studies on the association of the polymorphisms with LOAD risk in Han Chinese. Here, the association of TOMM40 polymorphisms in LOAD was investigated in a large Northern Han Chinese cohort consisting of 1,578 individuals. Both allelic and genotypic associations of three SNPs (rs157580, rs2075650, and rs11556505) with LOAD risk were observed in the total sample as well as in the non- APOE ε4 carriers. For rs1160985, the allele and genotype frequencies differed significantly only in APOE ε4 carriers. After adjustment for age, gender, and APOE ε4 status, the association remained statistically significant only for the rs157580 but not for rs2075650 and rs11556505. In contrast, the rs1160985 exhibited significant risk effect after adjustment. In addition, haplotype analysis confirmed that the haplotypes derived from SNPs in rs2075650, rs11556505, and rs1160985 were associated with either risk or protective effects. In summary, our findings suggest that the TOMM40 polymorphisms may play a role in the pathogenesis of LOAD in Han Chinese.

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Acknowledgments

We are grateful to all of the subjects who kindly agreed to participate in this study. This work was supported by grants from the National Natural Science Foundation of China (81000544, 81171209), the Shandong Provincial Natural Science Foundation, China (ZR2010HQ004, ZR2011HZ001), the Medicine and Health Science Technology Development Project of Shandong Province (2011WSA02018, 2011WSA02020), and the Shandong Provincial Outstanding Medical Academic Professional Program.

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Authors and Affiliations

  1. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao, 266071, China

    Xiao-Ying Ma, Jin-Tai Yu, Wei Wang, Hui-Fu Wang, Qiu-Yan Liu, Wei Zhang & Lan Tan

  2. College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 266003, China

    Jin-Tai Yu & Lan Tan

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  1. Xiao-Ying Ma
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  2. Jin-Tai Yu
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  4. Hui-Fu Wang
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  6. Wei Zhang
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  7. Lan Tan
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Correspondence to Jin-Tai Yu or Lan Tan.

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Ma, XY., Yu, JT., Wang, W. et al. Association of TOMM40 Polymorphisms with Late-Onset Alzheimer’s Disease in a Northern Han Chinese Population. Neuromol Med 15, 279–287 (2013). https://doi.org/10.1007/s12017-012-8217-7

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  • DOI: https://doi.org/10.1007/s12017-012-8217-7

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