Universität zu Köln

Duvvari, Maheswara R., Paun, Codrut C., Buitendijk, Gabrielle H. S., Saksens, Nicole T. M., Volokhina, Elena B., Ristau, Tina, Schoenmaker-Koller, Frederieke E., van de Ven, Johannes P. H., Groenewoud, Joannes M. M., van den Heuvel, Lambertus P. W. J., Hofman, Albert, Fauser, Sascha, Uitterlinden, Andre G., Klaver, Caroline C. W., Hoyng, Carel B., de Jong, Eiko K. and den Hollander, Anneke I. (2014). Analysis of Rare Variants in the C3 Gene in Patients with Age-Related Macular Degeneration. PLoS One, 9 (4). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Age-related macular degeneration (AMD) is a progressive retinal disorder affecting over 33 million people worldwide. Genome-wide association studies (GWASs) for AMD identified common variants at 19 loci accounting for 15-65% of the heritability and it has been hypothesized that the missing heritability may be attributed to rare variants with large effect sizes. Common variants in the complement component 3 (C3) gene have been associated with AMD and recently a rare C3 variant (Lys155Gln) was identified which exerts a large effect on AMD susceptibility independent of the common variants. To explore whether additional rare variants in the C3 gene are associated with AMD, we sequenced all coding exons in 84 unrelated AMD cases. Subsequently, we genotyped all identified variants in 1474 AMD cases and 2258 controls. Additionally, because of the known genetic overlap between AMD and atypical hemolytic uremic syndrome (aHUS), we genotyped two recurrent aHUS-associated C3 mutations in the entire cohort. Overall, we identified three rare variants (Lys65Gln (P = 0.04), Arg735Trp (OR = 17.4, 95% CI = 2.2-136; P = 0.0003), and Ser1619Arg (OR = 5.2, 95% CI = 1.0-25; P = 0.05) at the C3 locus that are associated with AMD in our EUGENDA cohort. However, the Arg735Trp and Ser1619Arg variants were not found to be associated with AMD in the Rotterdam Study. The Lys65Gln variant was only identified in patients from Nijmegen, the Netherlands, and thus may represent a region-specific AMD risk variant.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Duvvari, Maheswara R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Paun, Codrut C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Buitendijk, Gabrielle H. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Saksens, Nicole T. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Volokhina, Elena B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ristau, Tina UNSPECIFIED UNSPECIFIED UNSPECIFIED Schoenmaker-Koller, Frederieke E. UNSPECIFIED UNSPECIFIED UNSPECIFIED van de Ven, Johannes P. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Groenewoud, Joannes M. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED van den Heuvel, Lambertus P. W. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofman, Albert UNSPECIFIED UNSPECIFIED UNSPECIFIED Fauser, Sascha UNSPECIFIED UNSPECIFIED UNSPECIFIED Uitterlinden, Andre G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Klaver, Caroline C. W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoyng, Carel B. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Jong, Eiko K. UNSPECIFIED UNSPECIFIED UNSPECIFIED den Hollander, Anneke I. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-440635
DOI:	10.1371/journal.pone.0094165
Journal or Publication Title:	PLoS One
Volume:	9
Number:	4
Date:	2014
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HIGH-RISK; COMPLEMENT ACTIVATION; MUTATION; ALLELES; CONFERS; CELLS; CFH; DNA Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44063