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Complement component 3 (C3) haplotypes and risk of advanced age-related macular degeneration

Cited 54 time in Web of Science Cited 57 time in Scopus
Authors
Park, Kyu Hyung; Fridley, Brooke L; Ryu, Euijung; Tosakulwong, Nirubol; Edwards, Albert O
Issue Date
2009-02-24
Publisher
Association for Research in Vision and Ophthalmology (ARVO)
Citation
Invest Ophthalmol Vis Sci. 2009;50(7):3386-3393
Keywords
AgedAged, 80 and overAllelesComplement C3/*geneticsFemaleHaplotypes/*geneticsHumansLinkage DisequilibriumMacular Degeneration/*geneticsMalePolymorphism, Single Nucleotide/*geneticsRisk Factors
Abstract
PURPOSE: Nonsynonymous coding single nucleotide polymorphisms (nsSNPs) in complement component 3 (C3) alter the risk of age-related macular degeneration (AMD). This was a study of the effect of haplotypes across C3 on AMD risk. METHODS: Nine SNPs tagging haplotypes across C3 were genotyped on 738 subjects at the Mayo Clinic. Haplotype analyses were performed with and without conditioning on individual SNPs. Replication studies were performed using 1541 subjects from the age-related eye disease study (AREDS). RESULTS: Two nsSNPs located 5125 bp apart in the 5' end of C3 showed the highest association (rs1047286 or P314L, P = 9.2E-05; rs2230199 or R102G, P = 4.1E-05) with AMD. The minor alleles of both SNPs tagged a single risk haplotype. The effects of the two nsSNPs could not be distinguished due to high linkage disequilibrium. The risk SNPs preferentially promoted the development of advanced AMD relative to early AMD in both the Mayo and AREDS subjects. Haplotypes in the 3' end of the C3 locus were associated with AMD in both the Mayo and AREDS subjects. The effect persisted after conditioning on the nsSNPs only in the Mayo subjects. No interaction was found between rs2230199 and smoking or other AMD loci. CONCLUSIONS: nsSNPs in C3 increased the risk of developing AMD 1.8-fold for 1 risk allele or 2.4-fold for two risk alleles and were preferentially associated with advanced AMD. Further study is needed to determine whether haplotypes in the 3' end of C3 have an independent association with AMD.
ISSN
1552-5783 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19234341

http://www.iovs.org/cgi/reprint/50/7/3386.pdf

https://hdl.handle.net/10371/68333
DOI
https://doi.org/10.1167/iovs.08-3231
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College of Medicine/School of Medicine (의과대학/대학원)Ophthalmology (안과학전공)Journal Papers (저널논문_안과학전공)
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