Insulin-degrading enzyme and Alzheimer disease: A genetic association study in the Han Chinese

L. Bian, J. D. Yang, T. W. Guo, Y. Sun, S. W. Duan, W. Y. Chen, Y. X. Pan, G. Y. Feng, L. He

Research output: Contribution to journalArticle

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Abstract

Background: The gene for insulin-degrading enzyme (IDE) represents a strong positional and biologic candidate for late-onset Alzheimer disease (LOAD) susceptibility. IDE is located on chromosome 10q23.3 close to a region of linkage for LOAD. In addition, many studies have identified a possible role of IDE in the degradation of amyloid β-protein and the intracellular amyloid precursor protein (APP) domain released by γ-secretase processing. Objective: To examine the association of IDE with AD in the Han Chinese. Methods: Four IDE polymorphisms (three in 5′-untranslated region and one in intron 21) were analyzed, using a population of 210 patients with LOAD and 200 control subjects well matched for age, sex, and ethnic background. Results: Among the four polymorphisms studied, only the C allele of single-nucleotide polymorphism (SNP) IDE2 showed association with AD (p = 0.005). Stratification of the data by APOE ε4 status indicated that the association between IDE2 and AD was confined to APOE ε4 carriers only. No association was found between all variants studied and AD within APOE ε4-negative subjects. The global haplotype frequencies showed significant differences between AD patients and control subjects. Furthermore, overrepresentation of GCTG haplotype in the AD group was found. It may be a risk haplotype for AD. Conclusions: These results suggest a possible synergic interaction between IDE and APOE ε4 in the risk to develop late-onset sporadic AD. IDE might modify the effect of the APOE ε4 risk factor in the Han Chinese population.

Original languageEnglish (US)
Pages (from-to)241-245
Number of pages5
JournalNeurology
Volume63
Issue number2
StatePublished - Jul 27 2004
Externally publishedYes

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Insulysin
Genetic Association Studies
Alzheimer Disease
Haplotypes
Amyloidogenic Proteins
Amyloid Precursor Protein Secretases
5' Untranslated Regions
Disease Susceptibility
Amyloid
Introns
Population
Single Nucleotide Polymorphism
Chromosomes
Alleles

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Bian, L., Yang, J. D., Guo, T. W., Sun, Y., Duan, S. W., Chen, W. Y., ... He, L. (2004). Insulin-degrading enzyme and Alzheimer disease: A genetic association study in the Han Chinese. Neurology, 63(2), 241-245.

Insulin-degrading enzyme and Alzheimer disease : A genetic association study in the Han Chinese. / Bian, L.; Yang, J. D.; Guo, T. W.; Sun, Y.; Duan, S. W.; Chen, W. Y.; Pan, Y. X.; Feng, G. Y.; He, L.

In: Neurology, Vol. 63, No. 2, 27.07.2004, p. 241-245.

Research output: Contribution to journalArticle

Bian, L, Yang, JD, Guo, TW, Sun, Y, Duan, SW, Chen, WY, Pan, YX, Feng, GY & He, L 2004, 'Insulin-degrading enzyme and Alzheimer disease: A genetic association study in the Han Chinese', Neurology, vol. 63, no. 2, pp. 241-245.
Bian L, Yang JD, Guo TW, Sun Y, Duan SW, Chen WY et al. Insulin-degrading enzyme and Alzheimer disease: A genetic association study in the Han Chinese. Neurology. 2004 Jul 27;63(2):241-245.
Bian, L. ; Yang, J. D. ; Guo, T. W. ; Sun, Y. ; Duan, S. W. ; Chen, W. Y. ; Pan, Y. X. ; Feng, G. Y. ; He, L. / Insulin-degrading enzyme and Alzheimer disease : A genetic association study in the Han Chinese. In: Neurology. 2004 ; Vol. 63, No. 2. pp. 241-245.
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abstract = "Background: The gene for insulin-degrading enzyme (IDE) represents a strong positional and biologic candidate for late-onset Alzheimer disease (LOAD) susceptibility. IDE is located on chromosome 10q23.3 close to a region of linkage for LOAD. In addition, many studies have identified a possible role of IDE in the degradation of amyloid β-protein and the intracellular amyloid precursor protein (APP) domain released by γ-secretase processing. Objective: To examine the association of IDE with AD in the Han Chinese. Methods: Four IDE polymorphisms (three in 5′-untranslated region and one in intron 21) were analyzed, using a population of 210 patients with LOAD and 200 control subjects well matched for age, sex, and ethnic background. Results: Among the four polymorphisms studied, only the C allele of single-nucleotide polymorphism (SNP) IDE2 showed association with AD (p = 0.005). Stratification of the data by APOE ε4 status indicated that the association between IDE2 and AD was confined to APOE ε4 carriers only. No association was found between all variants studied and AD within APOE ε4-negative subjects. The global haplotype frequencies showed significant differences between AD patients and control subjects. Furthermore, overrepresentation of GCTG haplotype in the AD group was found. It may be a risk haplotype for AD. Conclusions: These results suggest a possible synergic interaction between IDE and APOE ε4 in the risk to develop late-onset sporadic AD. IDE might modify the effect of the APOE ε4 risk factor in the Han Chinese population.",
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AB - Background: The gene for insulin-degrading enzyme (IDE) represents a strong positional and biologic candidate for late-onset Alzheimer disease (LOAD) susceptibility. IDE is located on chromosome 10q23.3 close to a region of linkage for LOAD. In addition, many studies have identified a possible role of IDE in the degradation of amyloid β-protein and the intracellular amyloid precursor protein (APP) domain released by γ-secretase processing. Objective: To examine the association of IDE with AD in the Han Chinese. Methods: Four IDE polymorphisms (three in 5′-untranslated region and one in intron 21) were analyzed, using a population of 210 patients with LOAD and 200 control subjects well matched for age, sex, and ethnic background. Results: Among the four polymorphisms studied, only the C allele of single-nucleotide polymorphism (SNP) IDE2 showed association with AD (p = 0.005). Stratification of the data by APOE ε4 status indicated that the association between IDE2 and AD was confined to APOE ε4 carriers only. No association was found between all variants studied and AD within APOE ε4-negative subjects. The global haplotype frequencies showed significant differences between AD patients and control subjects. Furthermore, overrepresentation of GCTG haplotype in the AD group was found. It may be a risk haplotype for AD. Conclusions: These results suggest a possible synergic interaction between IDE and APOE ε4 in the risk to develop late-onset sporadic AD. IDE might modify the effect of the APOE ε4 risk factor in the Han Chinese population.

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