The SIRT2 polymorphism rs10410544 and risk of Alzheimer's disease in two Caucasian case-control cohorts

Letizia Polito; Patrick G Kehoe; Annalisa Davin; Luisa Benussi; Roberta Ghidoni; Giuliano Binetti; Pierluigi Quadri; Ugo Lucca; Mauro Tettamanti; Francesca Clerici; Silvia Bagnoli; Daniela Galimberti; Benedetta Nacmias; Sandro Sorbi; Antonio Guaita; Elio Scarpini; Claudio Mariani; Gianluigi Forloni; Diego Albani

doi:10.1016/j.jalz.2012.02.003

The SIRT2 polymorphism rs10410544 and risk of Alzheimer's disease in two Caucasian case-control cohorts

Letizia Polito, Patrick G Kehoe, Annalisa Davin, Luisa Benussi, Roberta Ghidoni, Giuliano Binetti, Pierluigi Quadri, Ugo Lucca, Mauro Tettamanti, Francesca Clerici, Silvia Bagnoli, Daniela Galimberti, Benedetta Nacmias, Sandro Sorbi, Antonio Guaita, Elio Scarpini, Claudio Mariani, Gianluigi Forloni, Diego Albani^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

41 Citations (Scopus)

Abstract

Background: Human sirtuins are a current hotspot for research in neurodegenerative disorders, including Alzheimer's disease (AD). This study investigated whether genetic variants in two members of the sirtuin family, SIRT2 and SIRT3, affected AD susceptibility.

Methods: A genetic case-control study was performed, comprising 534 probable AD cases and 638 nondemented control subjects from the north of Italy and Canton Ticino, Switzerland (discovery population). The study was focused on SIRT2 rs10410544, SIRT3 rs4980329, and SIRT3 rs536715 single nucleotide polymorphisms (SNPs). These SNPs were genotyped by real-time polymerase chain reaction allelic discrimination assay or restriction fragment length polymorphism. The SNPs rs7412 and rs429358, mapping within the apolipoprotein E (APOE) gene, were genotyped by real-time polymerase chain reaction allelic discrimination assay too. In a replication population comprising 756 AD cases and 847 nondemented control subjects, SIRT2 rs10410544, APOE rs7412, and APOE rs429358 were genotyped as mentioned previously.

Results: In the discovery population, we observed an association between SIRT2 rs10410544 T allele and AD (adjusted odds ratio [OR] = 1.23, 95% confidence interval [Cl]: 1.02-1.50, P = .02, after correction for sex, age, and APOE epsilon 4 genotype). The association between AD and SIRT2 rs10410544 T allele was only present in APOE epsilon 4 noncarriers (adjusted OR = 1.29, 95% CI: 1.03-1.61, P = .03). The replication study did not confirm this evidence. However, the combined analysis on the two cohorts detected the association (adjusted OR = 1.17, 95% CI: 1.02-1.35, P = .02), and only APOE epsilon 4 noncarriers were at risk (adjusted OR = 1.2, 95% CI: 1.02-1.43, P = .03).

Conclusions: The SIRT2 rs10410544 T allele deserves further investigation as a novel minor genetic risk factor for AD in the APOE epsilon 4-negative Caucasian population. (C) 2013 The Alzheimer's Association. All rights reserved.

Original language	English
Pages (from-to)	392-399
Number of pages	8
Journal	Alzheimer's and Dementia
Volume	9
Issue number	4
DOIs	https://doi.org/10.1016/j.jalz.2012.02.003
Publication status	Published - Jul 2013

Bibliographical note

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Groups and Themes

Cerebrovascular and Dementia Research Group

Keywords

Sirtuin
Alzheimer's disease
SIRT2
SIRT3
APOE
Genetics
E TYPE-4 ALLELE
APOLIPOPROTEIN-E
GENES
ONSET
NEUROPROTECTION
ASSOCIATION
FREQUENCIES
SIRTUINS
STATE

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Polito, L., Kehoe, P. G., Davin, A., Benussi, L., Ghidoni, R., Binetti, G., Quadri, P., Lucca, U., Tettamanti, M., Clerici, F., Bagnoli, S., Galimberti, D., Nacmias, B., Sorbi, S., Guaita, A., Scarpini, E., Mariani, C., Forloni, G., & Albani, D. (2013). The SIRT2 polymorphism rs10410544 and risk of Alzheimer's disease in two Caucasian case-control cohorts. Alzheimer's and Dementia, 9(4), 392-399. https://doi.org/10.1016/j.jalz.2012.02.003

@article{f0ec8e4551db440a83872faa8ffbd23e,

title = "The SIRT2 polymorphism rs10410544 and risk of Alzheimer's disease in two Caucasian case-control cohorts",

abstract = "Background: Human sirtuins are a current hotspot for research in neurodegenerative disorders, including Alzheimer's disease (AD). This study investigated whether genetic variants in two members of the sirtuin family, SIRT2 and SIRT3, affected AD susceptibility.Methods: A genetic case-control study was performed, comprising 534 probable AD cases and 638 nondemented control subjects from the north of Italy and Canton Ticino, Switzerland (discovery population). The study was focused on SIRT2 rs10410544, SIRT3 rs4980329, and SIRT3 rs536715 single nucleotide polymorphisms (SNPs). These SNPs were genotyped by real-time polymerase chain reaction allelic discrimination assay or restriction fragment length polymorphism. The SNPs rs7412 and rs429358, mapping within the apolipoprotein E (APOE) gene, were genotyped by real-time polymerase chain reaction allelic discrimination assay too. In a replication population comprising 756 AD cases and 847 nondemented control subjects, SIRT2 rs10410544, APOE rs7412, and APOE rs429358 were genotyped as mentioned previously.Results: In the discovery population, we observed an association between SIRT2 rs10410544 T allele and AD (adjusted odds ratio [OR] = 1.23, 95\% confidence interval [Cl]: 1.02-1.50, P = .02, after correction for sex, age, and APOE epsilon 4 genotype). The association between AD and SIRT2 rs10410544 T allele was only present in APOE epsilon 4 noncarriers (adjusted OR = 1.29, 95\% CI: 1.03-1.61, P = .03). The replication study did not confirm this evidence. However, the combined analysis on the two cohorts detected the association (adjusted OR = 1.17, 95\% CI: 1.02-1.35, P = .02), and only APOE epsilon 4 noncarriers were at risk (adjusted OR = 1.2, 95\% CI: 1.02-1.43, P = .03).Conclusions: The SIRT2 rs10410544 T allele deserves further investigation as a novel minor genetic risk factor for AD in the APOE epsilon 4-negative Caucasian population. (C) 2013 The Alzheimer's Association. All rights reserved.",

keywords = "Sirtuin, Alzheimer's disease, SIRT2, SIRT3, APOE, Genetics, E TYPE-4 ALLELE, APOLIPOPROTEIN-E, GENES, ONSET, NEUROPROTECTION, ASSOCIATION, FREQUENCIES, SIRTUINS, STATE",

author = "Letizia Polito and Kehoe, \{Patrick G\} and Annalisa Davin and Luisa Benussi and Roberta Ghidoni and Giuliano Binetti and Pierluigi Quadri and Ugo Lucca and Mauro Tettamanti and Francesca Clerici and Silvia Bagnoli and Daniela Galimberti and Benedetta Nacmias and Sandro Sorbi and Antonio Guaita and Elio Scarpini and Claudio Mariani and Gianluigi Forloni and Diego Albani",

year = "2013",

month = jul,

doi = "10.1016/j.jalz.2012.02.003",

language = "English",

volume = "9",

pages = "392--399",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "John Wiley and Sons Inc",

number = "4",

}

Polito, L, Kehoe, PG, Davin, A, Benussi, L, Ghidoni, R, Binetti, G, Quadri, P, Lucca, U, Tettamanti, M, Clerici, F, Bagnoli, S, Galimberti, D, Nacmias, B, Sorbi, S, Guaita, A, Scarpini, E, Mariani, C, Forloni, G & Albani, D 2013, 'The SIRT2 polymorphism rs10410544 and risk of Alzheimer's disease in two Caucasian case-control cohorts', Alzheimer's and Dementia, vol. 9, no. 4, pp. 392-399. https://doi.org/10.1016/j.jalz.2012.02.003

TY - JOUR

T1 - The SIRT2 polymorphism rs10410544 and risk of Alzheimer's disease in two Caucasian case-control cohorts

AU - Polito, Letizia

AU - Kehoe, Patrick G

AU - Davin, Annalisa

AU - Benussi, Luisa

AU - Ghidoni, Roberta

AU - Binetti, Giuliano

AU - Quadri, Pierluigi

AU - Lucca, Ugo

AU - Tettamanti, Mauro

AU - Clerici, Francesca

AU - Bagnoli, Silvia

AU - Galimberti, Daniela

AU - Nacmias, Benedetta

AU - Sorbi, Sandro

AU - Guaita, Antonio

AU - Scarpini, Elio

AU - Mariani, Claudio

AU - Forloni, Gianluigi

AU - Albani, Diego

PY - 2013/7

Y1 - 2013/7

N2 - Background: Human sirtuins are a current hotspot for research in neurodegenerative disorders, including Alzheimer's disease (AD). This study investigated whether genetic variants in two members of the sirtuin family, SIRT2 and SIRT3, affected AD susceptibility.Methods: A genetic case-control study was performed, comprising 534 probable AD cases and 638 nondemented control subjects from the north of Italy and Canton Ticino, Switzerland (discovery population). The study was focused on SIRT2 rs10410544, SIRT3 rs4980329, and SIRT3 rs536715 single nucleotide polymorphisms (SNPs). These SNPs were genotyped by real-time polymerase chain reaction allelic discrimination assay or restriction fragment length polymorphism. The SNPs rs7412 and rs429358, mapping within the apolipoprotein E (APOE) gene, were genotyped by real-time polymerase chain reaction allelic discrimination assay too. In a replication population comprising 756 AD cases and 847 nondemented control subjects, SIRT2 rs10410544, APOE rs7412, and APOE rs429358 were genotyped as mentioned previously.Results: In the discovery population, we observed an association between SIRT2 rs10410544 T allele and AD (adjusted odds ratio [OR] = 1.23, 95% confidence interval [Cl]: 1.02-1.50, P = .02, after correction for sex, age, and APOE epsilon 4 genotype). The association between AD and SIRT2 rs10410544 T allele was only present in APOE epsilon 4 noncarriers (adjusted OR = 1.29, 95% CI: 1.03-1.61, P = .03). The replication study did not confirm this evidence. However, the combined analysis on the two cohorts detected the association (adjusted OR = 1.17, 95% CI: 1.02-1.35, P = .02), and only APOE epsilon 4 noncarriers were at risk (adjusted OR = 1.2, 95% CI: 1.02-1.43, P = .03).Conclusions: The SIRT2 rs10410544 T allele deserves further investigation as a novel minor genetic risk factor for AD in the APOE epsilon 4-negative Caucasian population. (C) 2013 The Alzheimer's Association. All rights reserved.

AB - Background: Human sirtuins are a current hotspot for research in neurodegenerative disorders, including Alzheimer's disease (AD). This study investigated whether genetic variants in two members of the sirtuin family, SIRT2 and SIRT3, affected AD susceptibility.Methods: A genetic case-control study was performed, comprising 534 probable AD cases and 638 nondemented control subjects from the north of Italy and Canton Ticino, Switzerland (discovery population). The study was focused on SIRT2 rs10410544, SIRT3 rs4980329, and SIRT3 rs536715 single nucleotide polymorphisms (SNPs). These SNPs were genotyped by real-time polymerase chain reaction allelic discrimination assay or restriction fragment length polymorphism. The SNPs rs7412 and rs429358, mapping within the apolipoprotein E (APOE) gene, were genotyped by real-time polymerase chain reaction allelic discrimination assay too. In a replication population comprising 756 AD cases and 847 nondemented control subjects, SIRT2 rs10410544, APOE rs7412, and APOE rs429358 were genotyped as mentioned previously.Results: In the discovery population, we observed an association between SIRT2 rs10410544 T allele and AD (adjusted odds ratio [OR] = 1.23, 95% confidence interval [Cl]: 1.02-1.50, P = .02, after correction for sex, age, and APOE epsilon 4 genotype). The association between AD and SIRT2 rs10410544 T allele was only present in APOE epsilon 4 noncarriers (adjusted OR = 1.29, 95% CI: 1.03-1.61, P = .03). The replication study did not confirm this evidence. However, the combined analysis on the two cohorts detected the association (adjusted OR = 1.17, 95% CI: 1.02-1.35, P = .02), and only APOE epsilon 4 noncarriers were at risk (adjusted OR = 1.2, 95% CI: 1.02-1.43, P = .03).Conclusions: The SIRT2 rs10410544 T allele deserves further investigation as a novel minor genetic risk factor for AD in the APOE epsilon 4-negative Caucasian population. (C) 2013 The Alzheimer's Association. All rights reserved.

KW - Sirtuin

KW - Alzheimer's disease

KW - SIRT2

KW - SIRT3

KW - APOE

KW - Genetics

KW - E TYPE-4 ALLELE

KW - APOLIPOPROTEIN-E

KW - GENES

KW - ONSET

KW - NEUROPROTECTION

KW - ASSOCIATION

KW - FREQUENCIES

KW - SIRTUINS

KW - STATE

U2 - 10.1016/j.jalz.2012.02.003

DO - 10.1016/j.jalz.2012.02.003

M3 - Article (Academic Journal)

C2 - 22651940

SN - 1552-5260

VL - 9

SP - 392

EP - 399

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 4

ER -

The SIRT2 polymorphism rs10410544 and risk of Alzheimer's disease in two Caucasian case-control cohorts

Abstract

Bibliographical note

UN SDGs

Research Groups and Themes

Keywords

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