Lack of association between Alzheimer's disease and the promoter region polymorphisms of the nicastrin gene

Antonio Orlacchio; Toshitaka Kawarai; Mario Polidoro; Andrew D. Paterson; Ekaterina Rogaeva; Aldo Orlacchio; Peter H. St. George-Hyslop; Giorgio Bernardi

doi:10.1016/j.neulet.2004.03.044

Lack of association between Alzheimer's disease and the promoter region polymorphisms of the nicastrin gene

Antonio Orlacchio, Toshitaka Kawarai, Mario Polidoro, Andrew D. Paterson, Ekaterina Rogaeva, Aldo Orlacchio, Peter H. St. George-Hyslop, Giorgio Bernardi

Fondazione Santa Lucia

Research output: Contribution to journal › Article › peer-review

Abstract

The biological analysis of nicastrin (NCSTN) shows its crucial role in γ-cleavage of the amyloid precursor protein. Inhibition of NCSTN demonstrated altered γ-cleavage activity, suggesting its potential implication in Alzheimer's disease (AD). We sequenced the NCSTN gene promoter region and found two promoter single nucleotide polymorphisms (SNPs) at putative transcription binding sites, -796T/G and -1216C/A. The association study using the promoter SNPs showed no significant genetic effect upon the development of AD. Haplotype analysis with the promoter SNPs and coding SNPs demonstrated no significant difference between familial AD cases and controls. Moreover, the genotype of each promoter SNP did not have an association with age-at-onset in AD. Our investigation suggests that the two promoter SNPs are unrelated to the development of AD, however, further investigation at the promoter region of NCSTN may be necessary to address its potential implication of gene expression in AD.

Original language	English
Pages (from-to)	49-53
Number of pages	5
Journal	Neuroscience Letters
Volume	363
Issue number	1
DOIs	https://doi.org/10.1016/j.neulet.2004.03.044
Publication status	Published - Jun 3 2004

Keywords

Alzheimer's disease
Association study
Nicastrin gene
Promoter region
Single nucleotide polymorphisms

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/j.neulet.2004.03.044

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Lack of association between Alzheimer's disease and the promoter region polymorphisms of the nicastrin gene. / Orlacchio, Antonio; Kawarai, Toshitaka; Polidoro, Mario; Paterson, Andrew D.; Rogaeva, Ekaterina; Orlacchio, Aldo; St. George-Hyslop, Peter H.; Bernardi, Giorgio.

In: Neuroscience Letters, Vol. 363, No. 1, 03.06.2004, p. 49-53.

Research output: Contribution to journal › Article › peer-review

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title = "Lack of association between Alzheimer's disease and the promoter region polymorphisms of the nicastrin gene",

abstract = "The biological analysis of nicastrin (NCSTN) shows its crucial role in γ-cleavage of the amyloid precursor protein. Inhibition of NCSTN demonstrated altered γ-cleavage activity, suggesting its potential implication in Alzheimer's disease (AD). We sequenced the NCSTN gene promoter region and found two promoter single nucleotide polymorphisms (SNPs) at putative transcription binding sites, -796T/G and -1216C/A. The association study using the promoter SNPs showed no significant genetic effect upon the development of AD. Haplotype analysis with the promoter SNPs and coding SNPs demonstrated no significant difference between familial AD cases and controls. Moreover, the genotype of each promoter SNP did not have an association with age-at-onset in AD. Our investigation suggests that the two promoter SNPs are unrelated to the development of AD, however, further investigation at the promoter region of NCSTN may be necessary to address its potential implication of gene expression in AD.",

keywords = "Alzheimer's disease, Association study, Nicastrin gene, Promoter region, Single nucleotide polymorphisms",

author = "Antonio Orlacchio and Toshitaka Kawarai and Mario Polidoro and Paterson, {Andrew D.} and Ekaterina Rogaeva and Aldo Orlacchio and {St. George-Hyslop}, {Peter H.} and Giorgio Bernardi",

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AU - Orlacchio, Antonio

AU - Kawarai, Toshitaka

AU - Polidoro, Mario

AU - Paterson, Andrew D.

AU - Rogaeva, Ekaterina

AU - Orlacchio, Aldo

AU - St. George-Hyslop, Peter H.

AU - Bernardi, Giorgio

PY - 2004/6/3

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N2 - The biological analysis of nicastrin (NCSTN) shows its crucial role in γ-cleavage of the amyloid precursor protein. Inhibition of NCSTN demonstrated altered γ-cleavage activity, suggesting its potential implication in Alzheimer's disease (AD). We sequenced the NCSTN gene promoter region and found two promoter single nucleotide polymorphisms (SNPs) at putative transcription binding sites, -796T/G and -1216C/A. The association study using the promoter SNPs showed no significant genetic effect upon the development of AD. Haplotype analysis with the promoter SNPs and coding SNPs demonstrated no significant difference between familial AD cases and controls. Moreover, the genotype of each promoter SNP did not have an association with age-at-onset in AD. Our investigation suggests that the two promoter SNPs are unrelated to the development of AD, however, further investigation at the promoter region of NCSTN may be necessary to address its potential implication of gene expression in AD.

AB - The biological analysis of nicastrin (NCSTN) shows its crucial role in γ-cleavage of the amyloid precursor protein. Inhibition of NCSTN demonstrated altered γ-cleavage activity, suggesting its potential implication in Alzheimer's disease (AD). We sequenced the NCSTN gene promoter region and found two promoter single nucleotide polymorphisms (SNPs) at putative transcription binding sites, -796T/G and -1216C/A. The association study using the promoter SNPs showed no significant genetic effect upon the development of AD. Haplotype analysis with the promoter SNPs and coding SNPs demonstrated no significant difference between familial AD cases and controls. Moreover, the genotype of each promoter SNP did not have an association with age-at-onset in AD. Our investigation suggests that the two promoter SNPs are unrelated to the development of AD, however, further investigation at the promoter region of NCSTN may be necessary to address its potential implication of gene expression in AD.

KW - Alzheimer's disease

KW - Association study

KW - Nicastrin gene

KW - Promoter region

KW - Single nucleotide polymorphisms

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Lack of association between Alzheimer's disease and the promoter region polymorphisms of the nicastrin gene

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Keywords

ASJC Scopus subject areas

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