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Association of complement factor H Y402H gene polymorphism with Alzheimer's disease

Association of complement factor H Y402H gene polymorphism with Alzheimer's disease Alzheimer's disease (AD) and age‐related macular degeneration (AMD) share several epidemiological and biochemical features. The present study aimed to assess the possible influence of the AMD‐associated complement factor H (CFH) Y402H (1277T > C) polymorphism on the risk of AD. Caucasian subjects (n = 800) meeting the criteria for probable (n = 717) or definite (n = 83) AD and Caucasian non‐demented controls (n = 1265) were included in this multi‐center case‐control study, in which genotype and allele frequencies of the CFH 1277T > C polymorphism were determined and related to diagnosis, APOE genotype, Mini‐Mental State Examination score (MMSE) and the cerebrospinal fluid (CSF) biomarkers total‐tau (T‐tau), phospho‐tau181 (P‐tau181), and β‐amyloid1–42 (Aβ1–42). The AMD‐associated CFH genotypes (1277CC and 1277TC) were overrepresented in subjects with AD as compared to control individuals (P = 0.029). Positive C carrier status was associated with an odds ratio (OR) for AD of 1.24 (95% confidence interval (CI) 1.02–1.50). When APOE ε4 carrier status was included in the regression model, this association was even stronger (OR 1.34, 95% CI: 1.08–1.65, P = 0.007). Subgroup analysis showed that the association between CFH C allele positivity and AD was only evident for individuals carrying the APOE ε4 allele. Positive C carrier status was also associated with lower levels of CSF Aβ1–42 selectively in the control group in an APOE ε4‐independent manner (P = 0.003). In conclusion, the CFH 1277T > C polymorphism seems to influence the risk of AD and there appears to be an interaction between CFH 1277C and APOE ε4 alleles. The CFH 1277C allele may predispose patients for co‐morbidity in AD and AMD. © 2007 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Medical Genetics part B Wiley

Association of complement factor H Y402H gene polymorphism with Alzheimer's disease

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References (65)

Publisher
Wiley
Copyright
Copyright © 2007 Wiley‐Liss, Inc.
ISSN
1552-4841
eISSN
1552-485X
DOI
10.1002/ajmg.b.30668
pmid
18163432
Publisher site
See Article on Publisher Site

Abstract

Alzheimer's disease (AD) and age‐related macular degeneration (AMD) share several epidemiological and biochemical features. The present study aimed to assess the possible influence of the AMD‐associated complement factor H (CFH) Y402H (1277T > C) polymorphism on the risk of AD. Caucasian subjects (n = 800) meeting the criteria for probable (n = 717) or definite (n = 83) AD and Caucasian non‐demented controls (n = 1265) were included in this multi‐center case‐control study, in which genotype and allele frequencies of the CFH 1277T > C polymorphism were determined and related to diagnosis, APOE genotype, Mini‐Mental State Examination score (MMSE) and the cerebrospinal fluid (CSF) biomarkers total‐tau (T‐tau), phospho‐tau181 (P‐tau181), and β‐amyloid1–42 (Aβ1–42). The AMD‐associated CFH genotypes (1277CC and 1277TC) were overrepresented in subjects with AD as compared to control individuals (P = 0.029). Positive C carrier status was associated with an odds ratio (OR) for AD of 1.24 (95% confidence interval (CI) 1.02–1.50). When APOE ε4 carrier status was included in the regression model, this association was even stronger (OR 1.34, 95% CI: 1.08–1.65, P = 0.007). Subgroup analysis showed that the association between CFH C allele positivity and AD was only evident for individuals carrying the APOE ε4 allele. Positive C carrier status was also associated with lower levels of CSF Aβ1–42 selectively in the control group in an APOE ε4‐independent manner (P = 0.003). In conclusion, the CFH 1277T > C polymorphism seems to influence the risk of AD and there appears to be an interaction between CFH 1277C and APOE ε4 alleles. The CFH 1277C allele may predispose patients for co‐morbidity in AD and AMD. © 2007 Wiley‐Liss, Inc.

Journal

American Journal of Medical Genetics part B – Wiley

Published: Sep 5, 2008

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