mtDNA Polymorphisms in Japanese Sporadic Alzheimer’s Disease

doi:10.1016/S0197-4580(98)00028-1

Neurobiology of Aging

Volume 19, Issue 1, Supplement 1, January–February 1998, Pages S47-S51

https://doi.org/10.1016/S0197-4580(98)00028-1 Get rights and content

Abstract

We screened 92 Japanese patients with sporadic AD (clinically diagnosed: 72 cases; autopsy-confirmed: 20 cases) and 59 age-matched controls for mitochondrial polymorphisms previously reported to be associated with increased risk in Caucasian AD. The polymorphisms in tRNA^Gln (nt. 4336), 16S rRNA (nt. 3196), and ND1 (nt. 3397) were not found in either in Japanese AD or age-matched controls. The frequencies of these polymorphisms in Japanese seems to be very rare if not absent, indicating that these three mutations are not likely to be genetic risk factors of Japanese AD. In the analysis of polymorphisms of 12S rRNA, however, we identified two novel mutations, an insertion of three cytosines and an A to G transition at nt. 856, which have not been described before. The insertion of three cytosines was observed in one of the 90 AD cases, but not in 59 normal controls. The A to G transition at nt. 856 was found in 2 of the 90 AD cases, but not in 59 normal controls. These results raise the possibility that the mutations in the 12S rRNA are genetic risk factors for AD in Japanese population.

Section snippets

Materials

High molecular weight genomic DNA was extracted either from peripheral blood leukocytes of clinically diagnosed sporadic AD patients or from frozen cerebral cortex tissues from 20 Japanese patients with pathologically confirmed AD, as previously described [20]. High molecular weight genomic DNA was also obtained from 59 healthy Japanese age-matched controls. Clinical diagnosis of AD was made based on the NINCDS ADRDA criteria (probable AD) [10]. (Family histories were obtained through extensive

Polymorphism of tRNA^Gln4336 , ND I^{3397 (MetVal)}, and 16S rRNA³¹⁹⁶ Genes

In the screening of 92 Japanese patients with sporadic AD (clinically diagnosed: 72 cases; autopsy-confirmed: 20 cases) and 59 age-matched controls, polymorphism of tRNA^Gln4336, ND I^{3397 (MetVal)}, or 16S rRNA³¹⁹⁶ genes were not present in the AD patients or age-matched controls (Table 1).

Polymorphism of 12S rRNA Gene

We have screened 90 Japanese patients with sporadic AD (clinically diagnosed: 70 cases; autopsy-confirmed: 20 cases) and 59 age-matched controls for the 12S rRNA polymorphism. In one of the clinically defined

Discussion

In this study, we have screened 92 Japanese patients with sporadic AD and 59 age-matched controls for four mitochondrial polymorphisms. The polymorphisms in tRNA^Gln (nt. 4336), 16S rRNA (nt. 3196), and ND1 (nt. 3397) were not found in either in Japanese AD or age-matched controls. These results indicate that these three polymorphisms are not likely to be risk factors for AD in Japanese.

In 12S rRNA, however, we found one patient with an insertion of three cytosines at nt. 956 and 965, and two

Acknowledgements

This study was supported in part by a grant for Research for the Future Program from the Japan Society for the Promotion of Science (JSPS-RFTF96L00103), a Grant-in-Aid for Scientific Research on Priority Areas (Human Genome Program) from The Ministry of Education, Science, and Culture, Japan, a grant from Research Committee for Ataxic Diseases, the Ministry of Health and Welfare, Japan, a grant for Surveys and Research on Specific Diseases, the Ministry of Health and Welfare, Japan, special

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Original ArticlesmtDNA Polymorphisms in Japanese Sporadic Alzheimer’s Disease

Abstract

Section snippets

Materials

Polymorphism of tRNAGln4336 , ND I3397 (MetVal), and 16S rRNA3196 Genes

Polymorphism of 12S rRNA Gene

Discussion

Acknowledgements

Mol. Brain Res.

Am. J. Otolaryngol.

Genomics

J. Neurol. Sci.

Sequence and organization of the human mitochondrial genome

Nature

Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families

Science

Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease

Nature

A mitochondrial DNA clone is associated with increased risk for Alzheimer disease

Proc. Natl. Acad. Sci. USA

A molecular basis for human hypersensitivity to aminoglycoside antibiotics

Nucl. Acids Res.

Candidate gene for the chromosome 1 familial Alzheimer’s disease locus

Science

Original Articles
mtDNA Polymorphisms in Japanese Sporadic Alzheimer’s Disease

Polymorphism of tRNA^Gln4336 , ND I^{3397 (MetVal)}, and 16S rRNA³¹⁹⁶ Genes