The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk
Open accessAbstract
Common polymorphisms in complement alternative pathway (AP) proteins C3 (C3 R102G), factor B (fB R32Q), and factor H (fH V62I) are associated with age-related macular degeneration (AMD) and other pathologies. Our published work showed that fB R32Q influences C3 convertase formation, whereas fH V62I affects factor I cofactor activity. Here we show how C3 R102G(C3S/F) influences AP activity. In hemolysis assays, C3 102G activated AP more efficiently (EC 50 C3 102G: 157 nM; C3 102R: 191 nM;P< 0.0001). fB binding kinetics and convertase stability were identical, but native and recombinant fH bound more strongly to C3b 102R(KD C3b 102R: 1.0 μM; C3b 102G: 1.4 μM;P< 0.0001). Accelerated decay was unaltered, but fH cofactor activity was reduced for C3b 102G, favoring AP amplification. Combining disease “risk” variants (C3 102G, fB 32R, and fH 62V) in add-back assays yielded sixfold higher hemolytic activity compared with “protective” variants (C3 102R, fB 32Q, and fH 62I;P< 0.0001). These data introduce the concept of a functional complotype (combination of polymorphisms) defining complement activity in an individual, thereby influencing susceptibility to AP-driven disease.
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Cites
Complement factor H polymorphism in age-related macular degeneration
Klein, R. J., Zeiss, C., Chew, E. Y., Tsai, J.-Y., Sackler, R. S., Haynes, C., Henning, A. K., SanGiovanni, J. P., Mane, S. M., Mayne, S. T., et al. (2005) · Science · doi:10.1126/science.1109557 · Cited by 4,492
Complement factor H polymorphism and age-related macular degeneration
Edwards, A. O., Ritter, R., Abel, K. J., Manning, A., Panhuysen, C., & Farrer, L. A. (2005) · Science · doi:10.1126/science.1110189 · Cited by 2,449
Complement factor H variant increases the risk of age-related macular degeneration
Haines, J. L., Hauser, M. A., Schmidt, S., Scott, W. K., Olson, L. M., Gallins, P., Spencer, K. L., Kwan, S. Y., Noureddine, M., Gilbert, J. R., et al. (2005) · Science · doi:10.1126/science.1110359 · Cited by 2,424
Hageman, G. S., Anderson, D. H., Johnson, L. V., Hancox, L. S., Taiber, A. J., Hardisty, L. I., Hageman, J. L., Stockman, H. A., Borchardt, J. D., Gehrs, K. M., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501536102 · Cited by 1,961
The AMD Genetics Clinical Study Group, Gold, B., Merriam, J. E., Zernant, J., Hancox, L. S., Taiber, A. J., Gehrs, K., Cramer, K., Neel, J., Bergeron, J., et al. (2006) · Nature Genetics · doi:10.1038/ng1750 · Cited by 1,075
Complement C3 variant and the risk of age-related macular degeneration
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., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa072618 · Cited by 829
Variation near complement factor I is associated with risk of advanced AMD
Fagerness, J. A., Maller, J. B., Neale, B. M., Reynolds, R. C., Daly, M. J., & Seddon, J. M. (2009) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.140 · Cited by 357
Structural basis for complement factor H linked age-related macular degeneration
Prosser, B. E., Johnson, S., Roversi, P., Herbert, A. P., Blaum, B. S., Tyrrell, J., Jowitt, T. A., Clark, S. J., Tarelli, E., Uhrín, D., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20071069 · Cited by 184 · cited 2×
“The fH402H risk variant had no direct effect on fH AP regulation but influenced binding to sialylated surfaces (27, 28).”
BackgroundSobrin, L., Maller, J. B., Neale, B. M., Reynolds, R. C., Fagerness, J. A., Daly, M. J., & Seddon, J. M. (2010) · European Journal of Human Genetics · doi:10.1038/ejhg.2009.185 · Cited by 31
Cited by
Immunology of age-related macular degeneration
Ambati, J., Atkinson, J. P., & Gelfand, B. D. (2013) · Nature Reviews Immunology · doi:10.1038/nri3459 · Cited by 584
Membranoproliferative Glomerulonephritis — A New Look at an Old Entity
Sethi, S., & Fervenza, F. C. (2012) · New England Journal of Medicine · doi:10.1056/nejmra1108178 · Cited by 565
Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense
Ricklin, D., Reis, E. S., Mastellos, D. C., Gros, P., & Lambris, J. D. (2016) · Immunological Reviews · doi:10.1111/imr.12500 · Cited by 484
Complement, a target for therapy in inflammatory and degenerative diseases
Morgan, B. P., & Harris, C. L. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4657 · Cited by 431
Self-citationComplement and Its Receptors: New Insights into Human Disease
Holers, V. M. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120154 · Cited by 430
Metadata
- Authors
- Heurich, M., Martínez-Barricarte, R., Francis, N. J., Roberts, D. L., Rodríguez de Córdoba, S., Morgan, B. P., & Harris, C. L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2011-05-09
- Volume
- 108
- Issue
- 21
- Pages
- 8761-8766
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2131852221
- Cited by
- 231
- References
- 9
- FWCI
- 8.34
- Type
- journal article
- Language
- en
- Open access
- green
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- Heurich, M., Martínez-Barricarte, R., Francis, N. J., Roberts, D. L., Rodríguez de Córdoba, S., Morgan, B. P., & Harris, C. L. (2011). Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1019338108
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