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Katharina E. Schmid-Kubista, Nirubol Tosakulwong, Yanhong Wu, Euijung Ryu, Laura A. Hecker, Keith H. Baratz, William L. Brown, Albert O. Edwards; Copy Number Variation in Complement Factor H Related Genes and Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5234.
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To determine the contribution of copy number variation (CNV) in the regulation of complement activation (RCA) locus to the development of age-related macular degeneration (AMD).
A multiplex ligation-dependent probe amplification (MLPA) assay was developed to quantify the number of copies of CFH, CFHR3, CFHR1, CFHR4, CFHR2, and CFHR5 in humans. Subjects with (451) and without (362) AMD were genotyped using the assay and the impact on AMD risk was evaluated.
Nine different combinations of copy number variation were observed in the 813 subjects. Deletion of both CFHR3 and CFHR1 was protective (OR=0.47, 95% CI: 0.36-0.62) against AMD and was observed in 88 (19.5%) with AMD and 127 (35.1%) without AMD. The combined deletion of CFHR3 and CFHR1 was not independently associated with AMD after accounting for Y402H. Other deletions were much less common: CFHR1 and CFHR4 deletion (n=15, 1.9%), CFHR2 only deletion (n=7, 0.9%), CFHR3 only, CFH exon 18 only, and CFH intron 1 only deletion (each n=2, 0.2%), and combined CFHR3 and CFH exon 18 deletion as well as CFHR1 only deletion (each n=1, 0.1%). The combined CFHR3 and CFHR1 deletions were on a protective haplotype, while the CFHR1 and CFHR4 deletions were on neutral haplotypes.
We found copy number variations of CFHR3, CFHR1, CFHR4, and CFHR2 in Caucasians. Deletions of CFHR3 and CFHR1 alone and combined protect against the development of AMD. Deletion of CFHR4, alone and combined with CFHR1 does not seem to have an impact on AMD development.
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