DO: 0110021;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 19p13.3 | {Macular degeneration, age-related, 9} | 611378 | 3 | C3 | 120700 |
A number sign (#) is used with this entry because of evidence that susceptibility to age-related macular degeneration-9 (ARMD9) is conferred by variation in the C3 gene (120700) on chromosome 19p13.
For a phenotypic description and a discussion of genetic heterogeneity of age-related macular degeneration, see 603075.
Yates et al. (2007) genotyped SNPs spanning the complement genes C3 (120700) and C5 (120900) in 603 Caucasian English patients with age-related macular degeneration and 350 controls. They found that the common functional arg102-to-gly (R102G) polymorphism in the C3 gene (rs2230199; 120700.0001), which they referred to as R80G based on numbering that eliminated the 22 residues of the signal peptide, was strongly associated with ARMD (p = 5.9 x 10(-5)). The association was replicated in a Scottish group of 244 cases and 351 controls (p = 5.0 x 10(-5)). The 102R and 102G variants correspond to slow (C3S) and fast (C3F) electrophoretic allotypes, respectively. The odds ratio for ARMD in SF heterozygotes and FF homozygotes was 1.7 and 2.6, respectively, compared to SS homozygotes. The estimated population attributable risk for C3F was 22%.
Maller et al. (2007) likewise found association between the 102G variant and age-related macular degeneration.
Fritsche et al. (2013) identified association of the C allele of rs2230199 with increased risk of ARMD (OR 1.42, 95% CI 1.37-1.47, combined p = 1 x 10(-41)).
Seddon et al. (2013) sequenced the exons of 681 genes within all reported ARMD loci and related pathways in 2,493 cases. They genotyped 5,115 independent samples and confirmed association with ARMD of an allele in C3 encoding a lys155-to-gln variant (K155Q; 120700.0010) (rs147859257). Helgason et al. (2013) and Zhan et al. (2013) also found association of the K155Q variant in C3 with ARMD.
Fritsche, L. G., Chen, W., Schu, M., Yaspan, B. L., Yu, Y., Thorleifsson, G., Zack, D. J., Arakawa, S., Cipriani, V., Ripke, S., Igo, R. P., Jr., Buitendijk, G. H. S., and 144 others. Seven new loci associated with age-related macular degeneration. Nature Genet. 45: 433-439, 2013. [PubMed: 23455636] [Full Text: https://doi.org/10.1038/ng.2578]
Helgason, H., Sulem, P., Duvvari, M. R., Luo, H., Thorleifsson, G., Stefansson, H., Jonsdottir, I., Masson, G., Gudbjartsson, D. F., Walters, G. B., Magnusson, O. T., Kong, A., and 25 others. A rare nonsynonymous sequence variant in C3 is associated with high risk of age-related macular degeneration. Nature Genet. 45: 1371-1374, 2013. [PubMed: 24036950] [Full Text: https://doi.org/10.1038/ng.2740]
Maller, J. B., Fagerness, J. A., Reynolds, R. C., Neale, B. M., Daly, M. J., Seddon, J. M. Variation in complement factor 3 is associated with risk of age-related macular degeneration. Nature Genet. 39: 1200-1201, 2007. [PubMed: 17767156] [Full Text: https://doi.org/10.1038/ng2131]
Seddon, J. M., Yu, Y., Miller, E. C., Reynolds, R., Tan, P. L., Gowrisankar, S., Goldstein, J. I., Triebwasser, M., Anderson, H. E., Zerbib, J., Kavanagh, D., Souied, E., Katsanis, N., Daly, M. J., Atkinson, J. P., Raychaudhuri, S. Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration. Nature Genet. 45: 1366-1370, 2013. [PubMed: 24036952] [Full Text: https://doi.org/10.1038/ng.2741]
Yates, J. R. W., Sepp, T., Matharu, B. K., Khan, J. C., Thurlby, D. A., Shahid, H., Clayton, D. G., Hayward, C., Morgan, J., Wright, A. F., Armbrecht, A. M., Dhillon, B., Deary, I. J., Redmond, E., Bird, A. C., Moore, A. T. Complement C3 variant and the risk of age-related macular degeneration. New Eng. J. Med. 357: 553-561, 2007. [PubMed: 17634448] [Full Text: https://doi.org/10.1056/NEJMoa072618]
Zhan, X., Larson, D. E., Wang, C., Koboldt, D. C., Sergeev, Y. V., Fulton, R. S., Fulton, L. L., Fronick, C. C., Branham, K. E., Bragg-Gresham, J., Jun, G., Hu, Y, and 48 others. Identification of a rare coding variant in complement 3 associated with age-related macular degeneration. Nature Genet. 45: 1375-1379, 2013. [PubMed: 24036949] [Full Text: https://doi.org/10.1038/ng.2758]