Ethnic variation in AMD-associated complement factor H polymorphism p.Tyr402His

Michael A Grassi; John H Fingert; Todd E Scheetz; Benjamin R Roos; Robert Ritch; Sheila K West; Kazuhide Kawase; Abdirashid M Shire; Robert F Mullins; Edwin M Stone

doi:10.1002/humu.20359

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Ethnic variation in AMD-associated complement factor H polymorphism p.Tyr402His

Journal article

Open access

Peer reviewed

Ethnic variation in AMD-associated complement factor H polymorphism p.Tyr402His

Michael A Grassi, John H Fingert, Todd E Scheetz, Benjamin R Roos, Robert Ritch, Sheila K West, Kazuhide Kawase, Abdirashid M Shire, Robert F Mullins and Edwin M Stone

Human mutation, Vol.27(9), pp.921-925

09/2006

DOI: 10.1002/humu.20359

PMID: 16865697

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Abstract

Age-related macular degeneration (AMD) is the most common cause of irreversible visual loss in the developed world. Previous studies have demonstrated that the c.1204T>C, p.Tyr402His allelic variant in the complement factor H (CFH) gene is associated with an approximately three-fold increased risk for AMD in Caucasians of predominantly European descent. Both the prevalence as well as the phenotypic spectrum of AMD varies widely among persons of different ethnicities. We hypothesized that populations with a lower prevalence of AMD might also have a lower prevalence of the CFH risk allele. In this study we sought to determine the frequency of this sequence variant in control populations of Caucasians, African Americans, Hispanics, Somalis, and Japanese. Normal control populations were assembled for each ethnic group: Caucasian (n=148), Somali (n=128), African American (n=75), Hispanic (n=81), and Japanese (n=82). Individuals were genotyped using a restriction digest assay and the frequency of the C allele at nucleotide position 1204 of the CFH gene was determined. A bioinformatic approach was used to identify SNPs in linkage disequilibrium with rs1061170 (c.1204T>C, p.Tyr402His) from the human haplotype map project database (HapMap) in order to validate the findings. We found widely discordant frequencies of the risk allele between some of the different ethnic groups: Japanese 0.07+/-0.02, Hispanics 0.17+/-0.03, African-Americans 0.35+/-0.04, Caucasians 0.34+/-0.03, and Somalis 0.34+/-0.03. Allele frequencies generated by analysis of the HapMap database were consistent with these findings. This study suggests that there are other yet unidentified genetic factors important in the pathogenesis of AMD that may mitigate the effects of c.1204T>C, p.Tyr402His variant.

Haplotypes

European Continental Ancestry Group - genetics

Genetic Predisposition to Disease

Gene Frequency

Humans

Middle Aged

Risk Factors

Computational Biology

Histidine - genetics

Continental Population Groups - genetics

Macular Degeneration - diagnosis

Linkage Disequilibrium

Polymorphism, Genetic

Macular Degeneration - genetics

Alleles

Macular Degeneration - ethnology

Aged

Polymorphism, Single Nucleotide

Complement Factor H - genetics

Amino Acid Substitution

Tyrosine - genetics

Details

Title: Subtitle: Ethnic variation in AMD-associated complement factor H polymorphism p.Tyr402His
Creators: Michael A Grassi - Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City 52242, USA
John H Fingert
Todd E Scheetz
Benjamin R Roos
Robert Ritch
Sheila K West
Kazuhide Kawase
Abdirashid M Shire
Robert F Mullins
Edwin M Stone
Resource Type: Journal article
Publication Details: Human mutation, Vol.27(9), pp.921-925
DOI: 10.1002/humu.20359
PMID: 16865697
NLM abbreviation: Hum Mutat
ISSN: 1059-7794
eISSN: 1098-1004
Publisher: United States
Language: English
Date published: 09/2006
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983980071402771

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