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

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2008-09, Vol.147B (6), p.720-726
• Main Authors: Zetterberg, Madeleine, Landgren, Sara, Andersson, Malin E., Palmér, Mona Seibt, Gustafson, Deborah R., Skoog, Ingmar, Minthon, Lennart, Thelle, Dag S., Wallin, Anders, Bogdanovic, Nenad, Andreasen, Niels, Blennow, Kaj, Zetterberg, Henrik
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; age-related macular degeneration (AMD); Aged; Aged, 80 and over; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Amyloid beta-Peptides - cerebrospinal fluid; Apolipoprotein E4 - genetics; Biological and medical sciences; Case-Control Studies; Cohort Studies; Comorbidity; Complement Factor H - genetics; complement system; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; dementia; DNA Mutational Analysis; Female; Gene Frequency; Genetic Predisposition to Disease; genetics; Genotype; Histidine - genetics; Humans; inflammation; Macular Degeneration - cerebrospinal fluid; Macular Degeneration - epidemiology; Macular Degeneration - genetics; Male; Medical genetics; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Neurology; Ophthalmology; Organic mental disorders. Neuropsychology; Polymorphism, Single Nucleotide; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psykiatri; Retinopathies; tau Proteins - cerebrospinal fluid; Tyrosine - genetics
• ISSN: 1552-4841; 1552-485X; 1552-485X
• DOI: 10.1002/ajmg.b.30668

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.