TY - JOUR
T1 - Ubc9 gene polymorphisms and late-onset Alzheimer's disease in the Korean population
T2 - A genetic association study
AU - Ahn, Kyungsook
AU - Song, Ju Hee
AU - Kim, Doh Kwan
AU - Park, Moon Ho
AU - Jo, Sangmee A.
AU - Koh, Young Ho
N1 - Funding Information:
This study was supported by grants from the Ministry of Health, Welfare and Family Affairs and National Institute of Health Intramural Research Grant, Korea (4845-300-210-13; 4845-300-260)
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009/11/20
Y1 - 2009/11/20
N2 - Ubiquitin-conjugating enzyme E2I (Ubc9) ligates small ubiquitin-related modifier (SUMO) to target proteins, resulting in changes of their localization, activity, or stability. Sumoylation of amyloid precursor protein (APP) was reported to be associated with decreased levels of beta amyloid (Aβ) aggregates, suggesting that sumoylation may play a role in the pathogenesis of Alzheimer's disease (AD). We investigated the association between genetic variations of Ubc9 gene (UBE2I) and late-onset Alzheimer's disease (AD). Five single nucleotide polymorphisms (SNPs) in UBE2I were genotyped in the DNA samples of 312 AD patients, 347 subjects with mild cognitive impairment (MCI), and 489 cognitively healthy controls. The genotype distribution of a polymorphism in intron 7 (rs761059) differed between AD cases and controls, with an adjusted odds ratio (OR) of 1.45 (p = 0.046, 95% CI: 1.01-2.08). One haplotype (ht2 CAGAG) was found in 14.0% of the AD patients and in 11.1% of the controls (p = 0.04, OR = 1.43. 95% CI; 1.01-2.01). Stratification by the ApoE-ε4 allele gave no significant difference between the groups. When the samples were stratified by gender, the genotypes of two SNPs (rs8052688, rs8063) were significantly associated with the risk of MCI among women. Our investigation suggests that UBE2I polymorphisms might be associated with a risk of AD and MCI.
AB - Ubiquitin-conjugating enzyme E2I (Ubc9) ligates small ubiquitin-related modifier (SUMO) to target proteins, resulting in changes of their localization, activity, or stability. Sumoylation of amyloid precursor protein (APP) was reported to be associated with decreased levels of beta amyloid (Aβ) aggregates, suggesting that sumoylation may play a role in the pathogenesis of Alzheimer's disease (AD). We investigated the association between genetic variations of Ubc9 gene (UBE2I) and late-onset Alzheimer's disease (AD). Five single nucleotide polymorphisms (SNPs) in UBE2I were genotyped in the DNA samples of 312 AD patients, 347 subjects with mild cognitive impairment (MCI), and 489 cognitively healthy controls. The genotype distribution of a polymorphism in intron 7 (rs761059) differed between AD cases and controls, with an adjusted odds ratio (OR) of 1.45 (p = 0.046, 95% CI: 1.01-2.08). One haplotype (ht2 CAGAG) was found in 14.0% of the AD patients and in 11.1% of the controls (p = 0.04, OR = 1.43. 95% CI; 1.01-2.01). Stratification by the ApoE-ε4 allele gave no significant difference between the groups. When the samples were stratified by gender, the genotypes of two SNPs (rs8052688, rs8063) were significantly associated with the risk of MCI among women. Our investigation suggests that UBE2I polymorphisms might be associated with a risk of AD and MCI.
KW - Alzheimer's diseases
KW - MCI
KW - SNP
KW - UBC9
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U2 - 10.1016/j.neulet.2009.09.017
DO - 10.1016/j.neulet.2009.09.017
M3 - Article
C2 - 19765634
AN - SCOPUS:70349784876
VL - 465
SP - 272
EP - 275
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 3
ER -