title: Association of complement factor H Y402H gene polymorphism with Alzheimer's disease.
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) (Abeta(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 epsilon4 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 epsilon4 allele. Positive C carrier status was also associated with lower levels of CSF Abeta(1-42) selectively in the control group in an APOE epsilon4-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 epsilon4 alleles. The CFH 1277C allele may predispose patients for co-morbidity in AD and AMD.
authors.affiliation: Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Section of Ophthalmology, The Sahlgrenska Academy at Göteborg University, Mölndal, Sweden. madeleine.zetterberg@gu.se
authors.forename: Madeleine
authors.initials: M
authors.lastname: Zetterberg
authors.forename: Sara
authors.initials: S
authors.lastname: Landgren
authors.forename: Malin E
authors.initials: ME
authors.lastname: Andersson
authors.forename: Mona Seibt
authors.initials: MS
authors.lastname: Palmér
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Gustafson
authors.forename: Ingmar
authors.initials: I
authors.lastname: Skoog
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.forename: Dag S
authors.initials: DS
authors.lastname: Thelle
authors.forename: Anders
authors.initials: A
authors.lastname: Wallin
authors.forename: Nenad
authors.initials: N
authors.lastname: Bogdanovic
authors.forename: Niels
authors.initials: N
authors.lastname: Andreasen
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000453:epidemiology / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D015897:Comorbidity; D017242:Complement Factor H / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006639:Histidine / Q000235:genetics; D006801:Humans; D008268:Macular Degeneration / Q000134:cerebrospinal fluid / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014443:Tyrosine / Q000235:genetics; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D016875:tau Proteins; D014443:Tyrosine; D006639:Histidine; D017242:Complement Factor H