Complement factor H polymorphism p.Tyr402His and cuticular Drusen

Michael A Grassi; James C Folk; Todd E Scheetz; Christine M Taylor; Val C Sheffield; Edwin M Stone

doi:10.1001/archopht.125.1.93

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Complement factor H polymorphism p.Tyr402His and cuticular Drusen

Journal article

Open access

Peer reviewed

Complement factor H polymorphism p.Tyr402His and cuticular Drusen

Michael A Grassi, James C Folk, Todd E Scheetz, Christine M Taylor, Val C Sheffield and Edwin M Stone

Archives of ophthalmology (1960), Vol.125(1), pp.93-97

01/2007

DOI: 10.1001/archopht.125.1.93

PMID: 17210858

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Abstract

To determine the histidine frequency in patients with the cuticular drusen phenotype of age-related macular degeneration (AMD). Fifty individuals were identified who met the criteria for the cuticular drusen phenotype using a standard threshold photograph. We genotyped DNA samples using a polymerase chain reaction-based restriction digest assay. Seven hundred individuals with typical AMD and 252 controls were also genotyped. Fisher exact test was used to analyze the significance of allele frequency differences. The histidine variant was present in 70% (frequency +/- SE, 0.70 +/- 0.05) of the cuticular cohort, 55% (frequency +/- SE, 0.55 +/- 0.01) of the more typical AMD cases, and 34% (frequency +/- SE, 0.34 +/- 0.02) of controls. The association between the cuticular drusen phenotype and the histidine allele was highly significant (P = .003; odds ratio, 2.0; 95% confidence interval, 1.21-3.07; vs AMD cases P<.001; odds ratio 4.54; 95% confidence interval, 2.79-7.50; vs controls). Genotype distribution between the 3 groups was similarly significant (P<.001). The cuticular drusen phenotype is highly associated with the Tyr402His variant of the complement factor H (CFH) gene. The significantly higher histidine allele frequency in this group compared with the typical AMD cohort suggests that the complement cascade may play a greater role in the pathogenesis of the cuticular drusen subtype than in AMD as a whole. The c.1204T>C, p.Tyr402His allelic variant in the CFH gene is associated with a 3-fold increased risk for AMD. A high frequency of the histidine allele has also been noted in patients with membranoproliferative glomerulonephritis type II.

Polymerase Chain Reaction

Retinal Drusen - genetics

Humans

Middle Aged

Genotype

Male

Macular Degeneration - genetics

Aged, 80 and over

Adult

Female

Aged

Polymorphism, Single Nucleotide

Complement Factor H - genetics

Details

Title: Subtitle: Complement factor H polymorphism p.Tyr402His and cuticular Drusen
Creators: Michael A Grassi - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, USA
James C Folk
Todd E Scheetz
Christine M Taylor
Val C Sheffield
Edwin M Stone
Resource Type: Journal article
Publication Details: Archives of ophthalmology (1960), Vol.125(1), pp.93-97
DOI: 10.1001/archopht.125.1.93
PMID: 17210858
NLM abbreviation: Arch Ophthalmol
ISSN: 0003-9950
eISSN: 1538-3601
Publisher: American Medical Association; United States
Grant note: EY016822 / NEI NIH HHS
Language: English
Date published: 01/2007
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983979956602771

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