Genetic variants in the complement system predisposing to age-related macular degeneration: A review

Molecular Immunology

Volumn 61, Issue 2, 2014, Pages 118-125

  Schramm, Elizabeth C ^a   Clark, Simon J ^b   Triebwasser, Michael P ^a   Raychaudhuri, Soumya ^c,d,e,f   Seddon, Johanna M ^g,h   Atkinson, John P ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

^d LABORATORY FOR MOLECULAR MEDICINE   (United States)

^e BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^f UNIVERSITY OF MANCHESTER   (United Kingdom)

^g TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^h TUFTS MEDICAL CENTER   (United States)

Author keywords

Age related macular degeneration; Alternative pathway; Complement system; Genetic variants

Indexed keywords

ALTERNATIVE COMPLEMENT PATHWAY C3 C5 CONVERTASE; COMPLEMENT; COMPLEMENT COMPONENT C3; COMPLEMENT COMPONENT C9; COMPLEMENT FACTOR H; COMPLEMENT FACTOR I;

COMPLEMENT ALTERNATIVE PATHWAY; GENETIC ASSOCIATION; GENETIC PREDISPOSITION; GENETIC VARIABILITY; HUMAN; IMMUNOPATHOGENESIS; INNATE IMMUNITY; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; RETINA MACULA AGE RELATED DEGENERATION; RETINA NEOVASCULARIZATION; REVIEW;

AGE-RELATED MACULAR DEGENERATION; ALTERNATIVE PATHWAY; COMPLEMENT SYSTEM; GENETIC VARIANTS;

COMPLEMENT SYSTEM PROTEINS; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; HUMANS; MACULAR DEGENERATION;

EID: 84907598829     PISSN: 01615890     EISSN: 18729142     Source Type: Journal    
DOI: 10.1016/j.molimm.2014.06.032     Document Type: Review

References (67)

1. Abrera-Abeleda M.A., Nishimura C., Frees K., Jones M., Maga T., Katz L.M., Zhang Y., Smith R.J.H. Allelic variants of complement genes associated with dense deposit disease. J. Am. Soc. Nephrol.: JASN 2011, 22:1551-1559. 10.1681/ASN. 2010080795.
2. Ambati J., Atkinson J.P., Gelfand B.D. Immunology of age-related macular degeneration. Nat. Rev. Immunol. 2013, 13:438-451. 10.1038/nri3459.
3. Anderson D.H., Radeke M.J., Gallo N.B., Chapin E.A., Johnson P.T., Curletti C.R., Hancox L.S., Hu J., Ebright J.N., Malek G., Hauser M.A., Rickman C.B., Bok D., Hageman G.S., Johnson L.V. The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited. Prog. Retin. Eye Res. 2010, 29:95-112. 10.1016/j.preteyeres.2009.11.003.
4. Ansari M., McKeigue P.M., Skerka C., Hayward C., Rudan I., Vitart V., Polasek O., Armbrecht A.-M., Yates J.R.W., Vatavuk Z., Bencic G., Kolcic I., Oostra B.A., Van Duijn C.M., Campbell S., Stanton C.M., Huffman J., Shu X., Khan J.C., Shahid H., Harding S.P., Bishop P.N., Deary I.J., Moore A.T., Dhillon B., Rudan P., Zipfel P.F., Sim R.B., Hastie N.D., Campbell H., Wright A.F. Genetic influences on plasma CFH and CFHR1 concentrations and their role in susceptibility to age-related macular degeneration. Hum. Mol. Genet. 2013, 22:4857-4869. 10.1093/hmg/ddt336.
5. Avery R.L. The plague and macular degeneration. Ophthalmology 2010, 117:2442. 10.1016/j.ophtha.2010.08.052.
6. Bradley D.T., Zipfel P.F., Hughes A.E. Complement in age-related macular degeneration: a focus on function. Eye (Lond. Engl.) 2011, 25:683-693. 10.1038/eye.2011.37.
7. Cipriani V., Leung H.-T., Plagnol V., Bunce C., Khan J.C., Shahid H., Moore A.T., Harding S.P., Bishop P.N., Hayward C., Campbell S., Armbrecht A.M., Dhillon B., Deary I.J., Campbell H., Dunlop M., Dominiczak A.F., Mann S.S., Jenkins S.A., Webster A.R., Bird A.C., Lathrop M., Zelenika D., Souied E.H., Sahel J.-A., Léveillard T., French AMD Investigators, Cree A.J., Gibson J., Ennis S., Lotery A.J., Wright A.F., Clayton D.G., Yates J.R.W. Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB-FKBPL-NOTCH4 region of chromosome 6p21.3. Hum. Mol. Genet. 2012, 21:4138-4150. 10.1093/hmg/dds225.
8. Clark S.J., Bishop P.N., Day A.J. Complement factor H and age-related macular degeneration: the role of glycosaminoglycan recognition in disease pathology. Biochem. Soc. Trans. 2010, 38:1342-1348. 10.1042/BST0381342.
9. Clark S.J., Higman V.A., Mulloy B., Perkins S.J., Lea S.M., Sim R.B., Day A.J. His-384 allotypic variant of factor H associated with age-related macular degeneration has different heparin binding properties from the non-disease-associated form. J. Biol. Chem. 2006, 281:24713-24720. 10.1074/jbc.M605083200.
10. Clark S.J., Perveen R., Hakobyan S., Morgan B.P., Sim R.B., Bishop P.N., Day A.J. Impaired binding of the age-related macular degeneration-associated complement factor H 402H allotype to Bruch's membrane in human retina. J. Biol. Chem. 2010, 285:30192-30202. 10.1074/jbc.M110.103986.
11. Crabb J.W., Miyagi M., Gu X., Shadrach K., West K.A., Sakaguchi H., Kamei M., Hasan A., Yan L., Rayborn M.E., Salomon R.G., Hollyfield J.G. Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc. Nat. Acad. Sci. U.S.A. 2002, 99:14682-14687. 10.1073/pnas.222551899.
12. Day A.J., Willis A.C., Ripoche J., Sim R.B. Sequence polymorphism of human complement factor H. Immunogenetics 1988, 27:211-214.
13. Duvvari M.R., Paun C.C., Buitendijk G.H.S., Saksens N.T.M., Volokhina E.B., Ristau T., Schoenmaker-Koller F.E., van de Ven J.P.H., Groenewoud J.M.M., van den Heuvel L.P.W.J., Hofman A., Fauser S., Uitterlinden A.G., Klaver C.C.W., Hoyng C.B., de Jong E.K., den Hollander A.I. Analysis of rare variants in the c3 gene in patients with age-related macular degeneration. PLoS One 2014, 9:e94165. 10.1371/journal.pone.0094165.
14. Edwards A.O., Ritter R., Abel K.J., Manning A., Panhuysen C., Farrer L.A. Complement factor H polymorphism and age-related macular degeneration. Science 2005, 308:421-424. 10.1126/science.1110189.
15. Ennis S., Gibson J., Cree A.J., Collins A., Lotery A.J. Support for the involvement of complement factor I in age-related macular degeneration. Eur. J. Hum. Genet. 2010, 18:15-16. 10.1038/ejhg.2009.113.
16. Fagerness J.A., Maller J.B., Neale B.M., Reynolds R.C., Daly M.J., Seddon J.M. Variation near complement factor I is associated with risk of advanced AMD. Eur. J. Hum. Genet. 2009, 17:100-104. 10.1038/ejhg.2008.140.
17. Frémeaux-Bacchi V., Miller E.C., Liszewski M.K., Strain L., Blouin J., Brown A.L., Moghal N., Kaplan B.S., Weiss R.A., Lhotta K., Kapur G., Mattoo T., Nivet H., Wong W., Gie S., Hurault de Ligny B., Fischbach M., Gupta R., Hauhart R., Meunier V., Loirat C., Dragon-Durey M.-A., Fridman W.H., Janssen B.J.C., Goodship T.H.J., Atkinson J.P. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome. Blood 2008, 112:4948-4952. 10.1182/blood-2008-01-133702.
18. 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., Buitendijk G.H.S., Sim X., Weeks D.E., Guymer R.H., Merriam J.E., Francis P.J., Hannum G., Agarwal A., Armbrecht A.M., Audo I., Aung T., Barile G.R., Benchaboune M., Bird A.C., Bishop P.N., Branham K.E., Brooks M., Brucker A.J., Cade W.H., Cain M.S., Campochiaro P.A., Chan C.-C., Cheng C.-Y., Chew E.Y., Chin K.A., Chowers I., Clayton D.G., Cojocaru R., Conley Y.P., Cornes B.K., Daly M.J., Dhillon B., Edwards A.O., Evangelou E., Fagerness J., Ferreyra H.A., Friedman J.S., Geirsdottir A., George R.J., Gieger C., Gupta N., Hagstrom S.A., Harding S.P., Haritoglou C., Heckenlively J.R., Holz F.G., Hughes G., Ioannidis J.P.A., Ishibashi T., Joseph P., Jun G., Kamatani Y., Katsanis N., N Keilhauer C., Khan J.C., Kim I.K., Kiyohara Y., Klein B.E.K., Klein R., Kovach J.L., Kozak I., Lee C.J., Lee K.E., Lichtner P., Lotery A.J., Meitinger T., Mitchell P., Mohand-Saïd S., Moore A.T., Morgan D.J., Morrison M.A., Myers C.E., Naj A.C., Nakamura Y., Okada Y., Orlin A., Ortube M.C., Othman M.I., Pappas C., Park K.H., Pauer G.J.T., Peachey N.S., Poch O., Priya R.R., Reynolds R., Richardson A.J., Ripp R., Rudolph G., Ryu E., Sahel J.-A., Schaumberg D.A., Scholl H.P.N., Schwartz S.G., Scott W.K., Shahid H., Sigurdsson H., Silvestri G., Sivakumaran T.A., Smith R.T., Sobrin L., Souied E.H., Stambolian D.E., Stefansson H., Sturgill-Short G.M., Takahashi A., Tosakulwong N., Truitt B.J., Tsironi E.E., Uitterlinden A.G., van Duijn C.M., Vijaya L., Vingerling J.R., Vithana E.N., Webster A.R., Wichmann H.-E., Winkler T.W., Wong T.Y., Wright A.F., Zelenika D., Zhang M., Zhao L., Zhang K., Klein M.L., Hageman G.S., Lathrop G.M., Stefansson K., Allikmets R., Baird P.N., Gorin M.B., Wang J.J., Klaver C.C.W., Seddon J.M., Pericak-Vance M.A., Iyengar S.K., Yates J.R.W., Swaroop A., Weber B.H.F., Kubo M., Deangelis M.M., Léveillard T., Thorsteinsdottir U., Haines J.L., Farrer L.A., Heid I.M., Abecasis G.R., AMD Gene Consortium Seven new loci associated with age-related macular degeneration. Nat. Genet. 2013, 45:433-439. 439e1-439e2. 10.1038/ng.2578.
19. Fritsche L.G., Lauer N., Hartmann A., Stippa S., Keilhauer C.N., Oppermann M., Pandey M.K., Köhl J., Zipfel P.F., Weber B.H.F., Skerka C. An imbalance of human complement regulatory proteins CFHR1, CFHR3 and factor H influences risk for age-related macular degeneration (AMD). Hum. Mol. Genet. 2010, 19:4694-4704. 10.1093/hmg/ddq399.
20. Goicoechea de Jorge E., Caesar J.J.E., Malik T.H., Patel M., Colledge M., Johnson S., Hakobyan S., Morgan B.P., Harris C.L., Pickering M.C., Lea S.M. Dimerization of complement factor H-related proteins modulates complement activation in vivo. Proc. Nat. Acad. Sci. U.S.A. 2013, 110:4685-4690. 10.1073/pnas.1219260110.
21. Goicoechea de Jorge E., Harris C.L., Esparza-Gordillo J., Carreras L., Arranz E.A., Garrido C.A., López-Trascasa M., Sánchez-Corral P., Morgan B.P., Rodríguez de Córdoba S. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Proc. Nat. Acad. Sci. U.S.A. 2007, 104:240-245. 10.1073/pnas.0603420103.
22. Gold B., Merriam J.E., Zernant J., Hancox L.S., Taiber A.J., Gehrs K., Cramer K., Neel J., Bergeron J., Barile G.R., Smith R.T., AMD Genetics Clinical Study Group, Hageman G.S., Dean M., Allikmets R. Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nat. Genet. 2006, 38:458-462. 10.1038/ng1750.
23. Haapasalo K., Jarva H., Siljander T., Tewodros W., Vuopio-Varkila J., Jokiranta T.S. Complement factor H allotype 402H is associated with increased C3b opsonization and phagocytosis of Streptococcus pyogenes. Mol. Microbiol. 2008, 70:583-594. 10.1111/j.1365-2958.2008.06347.x.
24. 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., Smith R.J.H., Silvestri G., Russell S.R., Klaver C.C.W., Barbazetto I., Chang S., Yannuzzi L.A., Barile G.R., Merriam J.C., Smith R.T., Olsh A.K., Bergeron J., Zernant J., Merriam J.E., Gold B., Dean M., Allikmets R. A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc. Nat. Acad. Sci. U.S.A. 2005, 102:7227-7232. 10.1073/pnas.0501536102.
25. Hageman G.S., Hancox L.S., Taiber A.J., Gehrs K.M., Anderson D.H., Johnson L.V., Radeke M.J., Kavanagh D., Richards A., Atkinson J., Meri S., Bergeron J., Zernant J., Merriam J., Gold B., Allikmets R., Dean M. Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration: characterization, ethnic distribution and evolutionary implications. Ann. Med. 2006, 38:592-604. AMD Clinical Study Group.
26. Hageman G.S., Luthert P.J., Victor Chong N.H., Johnson L.V., Anderson D.H., Mullins R.F. An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch's membrane interface in aging and age-related macular degeneration. Prog. Retin. Eye Res. 2001, 20:705-732.
27. 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., Schnetz-Boutaud N., Agarwal A., Postel E.A., Pericak-Vance M.A. Complement factor H variant increases the risk of age-related macular degeneration. Science 2005, 308:419-421. 10.1126/science.1110359.
28. Hebecker M., Józsi M. Factor H-related protein 4 activates complement by serving as a platform for the assembly of alternative pathway C3 convertase via its interaction with C3b protein. J. Biol. Chem. 2012, 287:19528-19536. 10.1074/jbc.M112.364471.
29. 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., Rafnar T., Kiemeney L.A., Schoenmaker-Koller F.E., Zhao L., Boon C.J.F., Song Y., Fauser S., Pei M., Ristau T., Patel S., Liakopoulos S., van de Ven J.P.H., Hoyng C.B., Ferreyra H., Duan Y., Bernstein P.S., Geirsdottir A., Helgadottir G., Stefansson E., den Hollander A.I., Zhang K., Jonasson F., Sigurdsson H., Thorsteinsdottir U., Stefansson K. A rare nonsynonymous sequence variant in C3 is associated with high risk of age-related macular degeneration. Nat. Genet. 2013, 45:1371-1374. 10.1038/ng.2740.
30. Herbert A.P., Deakin J.A., Schmidt C.Q., Blaum B.S., Egan C., Ferreira V.P., Pangburn M.K., Lyon M., Uhrín D., Barlow P.N. Structure shows that a glycosaminoglycan and protein recognition site in factor H is perturbed by age-related macular degeneration-linked single nucleotide polymorphism. J. Biol. Chem. 2007, 282:18960-18968. 10.1074/jbc.M609636200.
31. Heurich M., Martínez-Barricarte R., Francis N.J., Roberts D.L., Rodríguez de Córdoba S., Morgan B.P., Harris C.L. Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk. Proc. Nat. Acad. Sci. U.S.A. 2011, 108:8761-8766. 10.1073/pnas.1019338108.
32. Hughes A.E., Orr N., Esfandiary H., Diaz-Torres M., Goodship T., Chakravarthy U. A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration. Nat. Genet. 2006, 38:1173-1177. 10.1038/ng1890.
33. Johnson L.V., Ozaki S., Staples M.K., Erickson P.A., Anderson D.H. A potential role for immune complex pathogenesis in drusen formation. Exp. Eye Res. 2000, 70:441-449. 10.1006/exer.1999.0798.
34. Józsi M., Heinen S., Hartmann A., Ostrowicz C.W., Hälbich S., Richter H., Kunert A., Licht C., Saunders R.E., Perkins S.J., Zipfel P.F., Skerka C. Factor H and atypical hemolytic uremic syndrome: mutations in the C-terminus cause structural changes and defective recognition functions. J. Am. Soc. Nephrol.: JASN 2006, 17:170-177. 10.1681/ASN. 2005080868.
35. Kavanagh D., Kemp E.J., Mayland E., Winney R.J., Duffield J.S., Warwick G., Richards A., Ward R., Goodship J.A., Goodship T.H.J. Mutations in complement factor I predispose to development of atypical hemolytic uremic syndrome. J. Am. Soc. Nephrol.: JASN 2005, 16:2150-2155. 10.1681/ASN.2005010103.
36. Kavanagh D., Richards A., Atkinson J. Complement regulatory genes and hemolytic uremic syndromes. Annu. Rev. Med. 2008, 59:293-309. 10.1146/annurev.med.59.060106.185110.
37. 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., Bracken M.B., Ferris F.L., Ott J., Barnstable C., Hoh J. Complement factor H polymorphism in age-related macular degeneration. Science 2005, 308:385-389. 10.1126/science.1109557.
38. Kondo N., Bessho H., Honda S., Negi A. Additional evidence to support the role of a common variant near the complement factor I gene in susceptibility to age-related macular degeneration. Eur. J. Hum. Genet. 2010, 18:634-635. 10.1038/ejhg.2009.243.
39. Lachmann P.J. The amplification loop of the complement pathways. Adv. Immunol. 2009, 104:115-149. 10.1016/S0065-2776(08)04004-2.
40. Lim L.S., Mitchell P., Seddon J.M., Holz F.G., Wong T.Y. Age-related macular degeneration. Lancet 2012, 379:1728-1738. 10.1016/S0140-6736(12)60282-7.
41. Liszewski M.K., Atkinson J.P. Too much of a good thing at the site of tissue injury: the instructive example of the complement system predisposing to thrombotic microangiopathy. Hematol. Am. Soc. Hematol. Educ. Program 2011, 2011:9-14. 10.1182/asheducation-2011.1.9.
42. Maller J., George S., Purcell S., Fagerness J., Altshuler D., Daly M.J., Seddon J.M. Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration. Nat. Genet. 2006, 38:1055-1059. 10.1038/ng1873.
43. 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. Nat. Genet. 2007, 39:1200-1201. 10.1038/ng2131.
44. Manuelian T., Hellwage J., Meri S., Caprioli J., Noris M., Heinen S., Jozsi M., Neumann H.P.H., Remuzzi G., Zipfel P.F. Mutations in factor H reduce binding affinity to C3b and heparin and surface attachment to endothelial cells in hemolytic uremic syndrome. J. Clin. Invest. 2003, 111:1181-1190. 10.1172/JCI16651.
45. Montes T., Tortajada A., Morgan B.P., Rodríguez de Córdoba S., Harris C.L. Functional basis of protection against age-related macular degeneration conferred by a common polymorphism in complement factor B. Proc. Nat. Acad. Sci. U.S.A. 2009, 106:4366-4371. 10.1073/pnas.0812584106.
46. Mullins R.F., Russell S.R., Anderson D.H., Hageman G.S. Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. FASEB J. 2000, 14:835-846. Off. Publ. Fed. Am. Soc. Exp. Biol.
47. Nishiguchi K.M., Yasuma T.R., Tomida D., Nakamura M., Ishikawa K., Kikuchi M., Ohmi Y., Niwa T., Hamajima N., Furukawa K., Terasaki H. C9-R95X polymorphism in patients with neovascular age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2012, 53:508-512. 10.1167/iovs.11-8425.
48. Noris M., Brioschi S., Caprioli J., Todeschini M., Bresin E., Porrati F., Gamba S., Remuzzi G. Familial haemolytic uraemic syndrome and an MCP mutation. Lancet 2003, 362:1542-1547. 10.1016/S0140-6736(03)14742-3.
49. Raychaudhuri S., Iartchouk O., Chin K., Tan P.L., Tai A.K., Ripke S., Gowrisankar S., Vemuri S., Montgomery K., Yu Y., Reynolds R., Zack D.J., Campochiaro B., Campochiaro P., Katsanis N., Daly M.J., Seddon J.M. A rare penetrant mutation in CFH confers high risk of age-related macular degeneration. Nat. Genet. 2011, 43:1232-1236. 10.1038/ng.976.
50. Raychaudhuri S., Ripke S., Li M., Neale B.M., Fagerness J., Reynolds R., Sobrin L., Swaroop A., Abecasis G., Seddon J.M., Daly M.J. Associations of CFHR1-CFHR3 deletion and a CFH SNP to age-related macular degeneration are not independent. Nat. Genet. 2010, 42:553-555. author reply 555-556. 10.1038/ng0710-553.
51. Richards A., Buddles M.R., Donne R.L., Kaplan B.S., Kirk E., Venning M.C., Tielemans C.L., Goodship J.A., Goodship T.H. Factor H mutations in hemolytic uremic syndrome cluster in exons 18-20, a domain important for host cell recognition. Am. J. Hum. Genet. 2001, 68:485-490. 10.1086/318203.
52. Richards A., Kemp E.J., Liszewski M.K., Goodship J.A., Lampe A.K., Decorte R., Müslümanoǧlu M.H., Kavukcu S., Filler G., Pirson Y., Wen L.S., Atkinson J.P., Goodship T.H.J. Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome. Proc. Nat. Acad. Sci. U.S.A. 2003, 100:12966-12971. 10.1073/pnas.2135497100.
53. Rudnicka A.R., Jarrar Z., Wormald R., Cook D.G., Fletcher A., Owen C.G. Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta-analysis. Ophthalmology 2012, 119:571-580. 10.1016/j.ophtha.2011.09.027.
54. Sánchez-Corral P., Pérez-Caballero D., Huarte O., Simckes A.M., Goicoechea E., López-Trascasa M., de Córdoba S.R. Structural and functional characterization of factor H mutations associated with atypical hemolytic uremic syndrome. Am. J. Hum. Genet. 2002, 71:1285-1295. 10.1086/344515.
55. 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. Nat. Genet. 2013, 45:1366-1370. 10.1038/ng.2741.
56. Sjöberg A.P., Trouw L.A., Clark S.J., Sjölander J., Heinegård D., Sim R.B., Day A.J., Blom A.M. The factor H variant associated with age-related macular degeneration (His-384) and the non-disease-associated form bind differentially to C-reactive protein, fibromodulin, DNA, and necrotic cells. J. Biol. Chem. 2007, 282:10894-10900. 10.1074/jbc.M610256200.
57. Sobrin L., Seddon J.M. Nature and nurture-genes and environment-predict onset and progression of macular degeneration. Prog. Retin. Eye Res. 2014, 40C:1-15. 10.1016/j.preteyeres.2013.12.004.
58. Sofat R., Casas J.P., Webster A.R., Bird A.C., Mann S.S., Yates J.R.W., Moore A.T., Sepp T., Cipriani V., Bunce C., Khan J.C., Shahid H., Swaroop A., Abecasis G., Branham K.E.H., Zareparsi S., Bergen A.A., Klaver C.C.W., Baas D.C., Zhang K., Chen Y., Gibbs D., Weber B.H.F., Keilhauer C.N., Fritsche L.G., Lotery A., Cree A.J., Griffiths H.L., Bhattacharya S.S., Chen L.L., Jenkins S.A., Peto T., Lathrop M., Leveillard T., Gorin M.B., Weeks D.E., Ortube M.C., Ferrell R.E., Jakobsdottir J., Conley Y.P., Rahu M., Seland J.H., Soubrane G., Topouzis F., Vioque J., Tomazzoli L., Young I., Whittaker J., Chakravarthy U., de Jong P.T.V.M., Smeeth L., Fletcher A., Hingorani A.D. Complement factor H genetic variant and age-related macular degeneration: effect size, modifiers and relationship to disease subtype. Int. J. Epidemiol. 2012, 41:250-262. 10.1093/ije/dyr204.
59. Thakkinstian A., McEvoy M., Chakravarthy U., Chakrabarti S., McKay G.J., Ryu E., Silvestri G., Kaur I., Francis P., Iwata T., Akahori M., Arning A., Edwards A.O., Seddon J.M., Attia J. The association between complement component 2/complement factor B polymorphisms and age-related macular degeneration: a HuGE review and meta-analysis. Am. J. Epidemiol. 2012, 176:361-372. 10.1093/aje/kws031.
60. Tortajada A., Yébenes H., Abarrategui-Garrido C., Anter J., García-Fernández J.M., Martínez-Barricarte R., Alba-Domínguez M., Malik T.H., Bedoya R., Cabrera Pérez R., López Trascasa M., Pickering M.C., Harris C.L., Sánchez-Corral P., Llorca O., Rodríguez de Córdoba S. C3 glomerulopathy-associated CFHR1 mutation alters FHR oligomerization and complement regulation. J. Clin. Invest. 2013, 123:2434-2446. 10.1172/JCI68280.
61. Van de Ven J.P.H., Nilsson S.C., Tan P.L., Buitendijk G.H.S., Ristau T., Mohlin F.C., Nabuurs S.B., Schoenmaker-Koller F.E., Smailhodzic D., Campochiaro P.A., Zack D.J., Duvvari M.R., Bakker B., Paun C.C., Boon C.J.F., Uitterlinden A.G., Liakopoulos S., Klevering B.J., Fauser S., Daha M.R., Katsanis N., Klaver C.C.W., Blom A.M., Hoyng C.B., den Hollander A.I. A functional variant in the CFI gene confers a high risk of age-related macular degeneration. Nat. Genet. 2013, 45:813-817. 10.1038/ng.2640.
62. Weismann D., Hartvigsen K., Lauer N., Bennett K.L., Scholl H.P.N., Charbel Issa P., Cano M., Brandstätter H., Tsimikas S., Skerka C., Superti-Furga G., Handa J.T., Zipfel P.F., Witztum J.L., Binder C.J. Complement factor H binds malondialdehyde epitopes and protects from oxidative stress. Nature 2011, 478:76-81. 10.1038/nature10449.
63. Wu J., Wu Y.-Q., Ricklin D., Janssen B.J.C., Lambris J.D., Gros P. Structure of complement fragment C3b-factor H and implications for host protection by complement regulators. Nat. Immunol. 2009, 10:728-733. 10.1038/ni.1755.
64. 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. N. Engl. J. Med. 2007, 357:553-561. Genetic Factors in AMD Study Group. 10.1056/NEJMoa072618.
65. Yehoshua Z., Alexandre de Amorim Garcia Filho C., Nunes R.P., Gregori G., Penha F.M., Moshfeghi A.A., Zhang K., Sadda S., Feuer W., Rosenfeld P.J. Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration. Ophthalmology 2014, 121:693-701. 10.1016/j.ophtha.2013.09.044.
66. Yu Y., Triebwasser M.P., Wong E.K.S., Schramm E.C., Thomas B., Reynolds R., Mardis E.R., Atkinson J.P., Daly M., Raychaudhuri S., Kavanagh D., Seddon J.M. Whole-exome sequencing identifies rare, functional CFH variants in families with macular degeneration. Hum. Mol. Genet. 2014, 10.1093/hmg/ddu226.
67. 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., Kang H.M., Liu D., Othman M., Brooks M., Ratnapriya R., Boleda A., Grassmann F., von Strachwitz C., Olson L.M., Buitendijk G.H.S., Hofman A., van Duijn C.M., Cipriani V., Moore A.T., Shahid H., Jiang Y., Conley Y.P., Morgan D.J., Kim I.K., Johnson M.P., Cantsilieris S., Richardson A.J., Guymer R.H., Luo H., Ouyang H., Licht C., Pluthero F.G., Zhang M.M., Zhang K., Baird P.N., Blangero J., Klein M.L., Farrer L.A., Deangelis M.M., Weeks D.E., Gorin M.B., Yates J.R.W., Klaver C.C.W., Pericak-Vance M.A., Haines J.L., Weber B.H.F., Wilson R.K., Heckenlively J.R., Chew E.Y., Stambolian D., Mardis E.R., Swaroop A., Abecasis G.R. Identification of a rare coding variant in complement 3 associated with age-related macular degeneration. Nat. Genet. 2013, 45:1375-1379. 10.1038/ng.2758.