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Association of complement factor HY402H gene polymorphism with Alzheimer's disease

Zetterberg, Madeleine; Landgren, Sara; Andersson, Malin E.; Palmer, Mona Seibt; Gustafson, Deborah R.; Skoog, Ingmar; Minthon, Lennart LU ; Thelle, Dag S.; Wallin, Anders and Bogdanovic, Nenad, et al. (2008) In American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 147B(6). p.720-726
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-tau(181),... (More)
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-tau(181), (P-tau(181)), and beta-amyloid(1-42) (A beta(1-42)). 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 4 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 epsilon 4 allele. Positive C carrier status was also associated with lower levels of CSF A beta(1-42) selectively in the control group in an APOE epsilon 4-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 epsilon 4 alleles. The CFH 1277C allele may predispose patients for co-morbidity in AD and AMD. (c) 2007 Wiley-Liss, Inc. (Less)
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published
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keywords
age-related macular degreneration (AMD), complement system, dementia, genetics, inflammation
in
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
volume
147B
issue
6
pages
720 - 726
publisher
International Society of Psychiatric Genetics
external identifiers
  • wos:000259050100008
  • scopus:51449085961
ISSN
1552-4841
DOI
10.1002/ajmg.b.30668
language
English
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yes
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f2691614-08bd-4a77-aeab-9875b82988dc (old id 1247117)
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2008-11-12 11:41:37
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2017-09-10 03:50:12
@article{f2691614-08bd-4a77-aeab-9875b82988dc,
  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-tau(181), (P-tau(181)), and beta-amyloid(1-42) (A beta(1-42)). 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 4 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 epsilon 4 allele. Positive C carrier status was also associated with lower levels of CSF A beta(1-42) selectively in the control group in an APOE epsilon 4-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 epsilon 4 alleles. The CFH 1277C allele may predispose patients for co-morbidity in AD and AMD. (c) 2007 Wiley-Liss, Inc.},
  author       = {Zetterberg, Madeleine and Landgren, Sara and Andersson, Malin E. and Palmer, Mona Seibt and Gustafson, Deborah R. and Skoog, Ingmar and Minthon, Lennart and Thelle, Dag S. and Wallin, Anders and Bogdanovic, Nenad and Andreasen, Niels and Blennow, Kaj and Zetterberg, Henrik},
  issn         = {1552-4841},
  keyword      = {age-related macular degreneration (AMD),complement system,dementia,genetics,inflammation},
  language     = {eng},
  number       = {6},
  pages        = {720--726},
  publisher    = {International Society of Psychiatric Genetics},
  series       = {American Journal of Medical Genetics Part B: Neuropsychiatric Genetics},
  title        = {Association of complement factor HY402H gene polymorphism with Alzheimer's disease},
  url          = {http://dx.doi.org/10.1002/ajmg.b.30668},
  volume       = {147B},
  year         = {2008},
}