TOMM40 and APOE Gene Expression and Cognitive Decline in Japanese Alzheimer's Disease Subjects
TOMM40 is located on chromosome 19, is in linkage disequilibrium with apolipoprotein E (APOE), andis reported in several genome-wide association studies to be associated with Alzheimer's disease (AD). Assess APOE and TOM40 and mitochondrial genes as blood biomarkers for AD. We examined TOMM40,...
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| Vydáno v: | Journal of Alzheimer's disease Ročník 60; číslo 3; s. 1107 |
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| Médium: | Journal Article |
| Jazyk: | angličtina |
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Netherlands
01.01.2017
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| ISSN: | 1875-8908, 1875-8908 |
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| Abstract | TOMM40 is located on chromosome 19, is in linkage disequilibrium with apolipoprotein E (APOE), andis reported in several genome-wide association studies to be associated with Alzheimer's disease (AD).
Assess APOE and TOM40 and mitochondrial genes as blood biomarkers for AD.
We examined TOMM40, PTEN-induced putative kinase 1 (PINK1), Parkin RBR E3 ubiquitin protein ligase (PARK2), and APOE mRNA expression in relation to the methylation rates of CpG sites in the upstream region of TOMM40exon 1 in peripheral leukocytes and TOMM40523 polyT genotypes in 60 AD and age- and sex-matched control subjects.
TOMM40 mRNA expression was significantly lower in AD subjects (0.87±0.18 versus 1.0±0.23, p = 0.005), and PINK1 mRNA expression was higher in AD subjects (1.5±0.61 versus 1.0±0.52, p < 0.001). TOMM40 mRNA expression was significantly correlated with the Mini-Mental State Examination total score (r = 0.290, p = 0.027). There was no expressional change in peripheral APOE mRNA in either AD or control subjects (p = 0.32). Methylation rates in the upstream region of TOMM40exon 1 were not different between AD and control subjects (average rate: 1.37±0.99 versus 1.39±1.20, p = 0.885), and TOMM40523 polyT genotypes were also not different between AD and control subjects (p = 0.67).
TOMM40 mRNA expression was lower in AD subjects and was correlated with cognitive decline. Significant changes in both TOMM40 and PINK1 mRNA may be related to mitochondrial dysfunction. |
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| AbstractList | TOMM40 is located on chromosome 19, is in linkage disequilibrium with apolipoprotein E (APOE), andis reported in several genome-wide association studies to be associated with Alzheimer's disease (AD).
Assess APOE and TOM40 and mitochondrial genes as blood biomarkers for AD.
We examined TOMM40, PTEN-induced putative kinase 1 (PINK1), Parkin RBR E3 ubiquitin protein ligase (PARK2), and APOE mRNA expression in relation to the methylation rates of CpG sites in the upstream region of TOMM40exon 1 in peripheral leukocytes and TOMM40523 polyT genotypes in 60 AD and age- and sex-matched control subjects.
TOMM40 mRNA expression was significantly lower in AD subjects (0.87±0.18 versus 1.0±0.23, p = 0.005), and PINK1 mRNA expression was higher in AD subjects (1.5±0.61 versus 1.0±0.52, p < 0.001). TOMM40 mRNA expression was significantly correlated with the Mini-Mental State Examination total score (r = 0.290, p = 0.027). There was no expressional change in peripheral APOE mRNA in either AD or control subjects (p = 0.32). Methylation rates in the upstream region of TOMM40exon 1 were not different between AD and control subjects (average rate: 1.37±0.99 versus 1.39±1.20, p = 0.885), and TOMM40523 polyT genotypes were also not different between AD and control subjects (p = 0.67).
TOMM40 mRNA expression was lower in AD subjects and was correlated with cognitive decline. Significant changes in both TOMM40 and PINK1 mRNA may be related to mitochondrial dysfunction. TOMM40 is located on chromosome 19, is in linkage disequilibrium with apolipoprotein E (APOE), andis reported in several genome-wide association studies to be associated with Alzheimer's disease (AD).BACKGROUNDTOMM40 is located on chromosome 19, is in linkage disequilibrium with apolipoprotein E (APOE), andis reported in several genome-wide association studies to be associated with Alzheimer's disease (AD).Assess APOE and TOM40 and mitochondrial genes as blood biomarkers for AD.OBJECTIVEAssess APOE and TOM40 and mitochondrial genes as blood biomarkers for AD.We examined TOMM40, PTEN-induced putative kinase 1 (PINK1), Parkin RBR E3 ubiquitin protein ligase (PARK2), and APOE mRNA expression in relation to the methylation rates of CpG sites in the upstream region of TOMM40exon 1 in peripheral leukocytes and TOMM40523 polyT genotypes in 60 AD and age- and sex-matched control subjects.METHODSWe examined TOMM40, PTEN-induced putative kinase 1 (PINK1), Parkin RBR E3 ubiquitin protein ligase (PARK2), and APOE mRNA expression in relation to the methylation rates of CpG sites in the upstream region of TOMM40exon 1 in peripheral leukocytes and TOMM40523 polyT genotypes in 60 AD and age- and sex-matched control subjects.TOMM40 mRNA expression was significantly lower in AD subjects (0.87±0.18 versus 1.0±0.23, p = 0.005), and PINK1 mRNA expression was higher in AD subjects (1.5±0.61 versus 1.0±0.52, p < 0.001). TOMM40 mRNA expression was significantly correlated with the Mini-Mental State Examination total score (r = 0.290, p = 0.027). There was no expressional change in peripheral APOE mRNA in either AD or control subjects (p = 0.32). Methylation rates in the upstream region of TOMM40exon 1 were not different between AD and control subjects (average rate: 1.37±0.99 versus 1.39±1.20, p = 0.885), and TOMM40523 polyT genotypes were also not different between AD and control subjects (p = 0.67).RESULTSTOMM40 mRNA expression was significantly lower in AD subjects (0.87±0.18 versus 1.0±0.23, p = 0.005), and PINK1 mRNA expression was higher in AD subjects (1.5±0.61 versus 1.0±0.52, p < 0.001). TOMM40 mRNA expression was significantly correlated with the Mini-Mental State Examination total score (r = 0.290, p = 0.027). There was no expressional change in peripheral APOE mRNA in either AD or control subjects (p = 0.32). Methylation rates in the upstream region of TOMM40exon 1 were not different between AD and control subjects (average rate: 1.37±0.99 versus 1.39±1.20, p = 0.885), and TOMM40523 polyT genotypes were also not different between AD and control subjects (p = 0.67).TOMM40 mRNA expression was lower in AD subjects and was correlated with cognitive decline. Significant changes in both TOMM40 and PINK1 mRNA may be related to mitochondrial dysfunction.CONCLUSIONTOMM40 mRNA expression was lower in AD subjects and was correlated with cognitive decline. Significant changes in both TOMM40 and PINK1 mRNA may be related to mitochondrial dysfunction. |
| Author | Sao, Tomoko Ochi, Shinichiro Iga, Jun-Ichi Yoshino, Yuta Ueno, Shu-Ichi Yamazaki, Kiyohiro Ozaki, Yuki Mori, Takaaki Mori, Yoko Mise, Ayano Yoshida, Taku |
| Author_xml | – sequence: 1 givenname: Ayano surname: Mise fullname: Mise, Ayano organization: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan – sequence: 2 givenname: Yuta surname: Yoshino fullname: Yoshino, Yuta organization: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan – sequence: 3 givenname: Kiyohiro surname: Yamazaki fullname: Yamazaki, Kiyohiro organization: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan – sequence: 4 givenname: Yuki surname: Ozaki fullname: Ozaki, Yuki organization: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan – sequence: 5 givenname: Tomoko surname: Sao fullname: Sao, Tomoko organization: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan – sequence: 6 givenname: Taku surname: Yoshida fullname: Yoshida, Taku organization: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan – sequence: 7 givenname: Takaaki surname: Mori fullname: Mori, Takaaki organization: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan – sequence: 8 givenname: Yoko surname: Mori fullname: Mori, Yoko organization: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan – sequence: 9 givenname: Shinichiro surname: Ochi fullname: Ochi, Shinichiro organization: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan – sequence: 10 givenname: Jun-Ichi surname: Iga fullname: Iga, Jun-Ichi organization: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan – sequence: 11 givenname: Shu-Ichi surname: Ueno fullname: Ueno, Shu-Ichi organization: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan |
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| Keywords | Parkin RBR E3 ubiquitin protein ligase (PARK2) PTEN-induced putative kinase 1 (PINK1) translocase of outer mitochondrial membrane 40 (TOMM40) Alzheimer’s disease apolipoprotein E (ApoE) methylation mitochondria mRNA expression |
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| Snippet | TOMM40 is located on chromosome 19, is in linkage disequilibrium with apolipoprotein E (APOE), andis reported in several genome-wide association studies to be... |
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| SubjectTerms | Aged Alzheimer Disease - blood Alzheimer Disease - genetics Apolipoproteins E - blood Biomarkers - blood Cognitive Dysfunction - blood Cognitive Dysfunction - genetics CpG Islands DNA Methylation Female Gene Expression Humans Japan Male Membrane Transport Proteins - blood Membrane Transport Proteins - genetics Mental Status Schedule Protein Kinases - blood RNA, Messenger - blood Ubiquitin-Protein Ligases - blood |
| Title | TOMM40 and APOE Gene Expression and Cognitive Decline in Japanese Alzheimer's Disease Subjects |
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