| H00821 | |
| H number | H00821 |
| Name | Age-related macular degeneration |
| Description | Macular degeneration is the physical breakdown of the central portion of the retina called the macula. Age-related macular degeneration (AMD/ARMD) is the leading cause of blindness. AMD is a complex disease caused by the combination of genetic predisposition and environmental factors. Using genome linkage scan and association studies, multiple potentially causative genes have been identified. In AMD, there are two phenotypes, atrophic/ dry and neovascular/ wet. The former is characterized by the geographic atrophy due to death of retinal pigment epithelium, and the latter is usually characterized by the abnormal growth of new blood vessels under the macula, which causes severe loss of vision. While wet AMD can be treated by the inhibition of vascular endothelial growth factor or photodynamic therapy, so far there are no available treatments for dry AMD. |
| Category | Nervous system disease |
| Network | nt06513(H00821) Complement cascade nt06517(H00821) TLR signaling nt06527(H00821) Necroptosis |
| Gene | (ARMD1) HMCN1 [HSA:83872] [KO:K17341] (ARMD1) CFHR1 [HSA:3078] [KO:K23815] (ARMD1) CFHR3 [HSA:10878] [KO:K23815] (ARMD2) ABCA4 [HSA:24] [KO:K05644] (ARMD3) FBLN5 [HSA:10516] [KO:K17340] (ARMD4) CFH [HSA:3075] [KO:K04004] (ARMD5) ERCC6 [HSA:2074] [KO:K10841] (ARMD6) RAX2 [HSA:84839] [KO:K09333] (ARMD7) HTRA1 [HSA:5654] [KO:K08784] (ARMD8) ARMS2 [HSA:387715] [KO:K25179] (ARMD9) C3 [HSA:718] [KO:K03990] (ARMD10) TLR4 [HSA:7099] [KO:K10160] (ARMD11) CST3 [HSA:1471] [KO:K13899] (ARMD12) CX3CR1 [HSA:1524] [KO:K04192] (ARMD13) CFI [HSA:3426] [KO:K01333] (ARMD14) C2 [HSA:717] [KO:K01332] (ARMD14) CFB [HSA:629] [KO:K01335] (ARMD15) C9 [HSA:735] [KO:K04000] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | Aflibercept [DR:D09574] Verteporfin [DR:D01162] Ranibizumab [DR:D05697] Brolucizumab [DR:D11083] Faricimab [DR:D11516] Avacincaptad pegol sodium [DR:D11748] |
| Comment | A haplotype carrying deletion of the complement factor H-related genes CFHR1 and CFHR3 is also associated with reduced risk of ARMD. |
| Other DBs | ICD-11: 9B75.0 ICD-10: H35.3 MeSH: D008268 OMIM: 603075 153800 608895 610698 613761 613757 610149 613778 611378 611488 611953 613784 615439 615489 615591 |
| Reference | PMID:18097986 AUTHORS Montezuma SR, Sobrin L, Seddon JM TITLE Review of genetics in age related macular degeneration. JOURNAL Semin Ophthalmol 22:229-40 (2007) DOI:10.1080/08820530701745140 PMID:17636773 AUTHORS Virgili G, Bini A TITLE Laser photocoagulation for neovascular age-related macular degeneration. JOURNAL Cochrane Database Syst Rev CD004763 (2007) DOI:10.1002/14651858.CD004763.pub2 PMID:14570714 (HMCN1) AUTHORS Schultz DW, Klein ML, Humpert AJ, Luzier CW, Persun V, Schain M, Mahan A, Runckel C, Cassera M, Vittal V, Doyle TM, Martin TM, Weleber RG, Francis PJ, Acott TS TITLE Analysis of the ARMD1 locus: evidence that a mutation in HEMICENTIN-1 is associated with age-related macular degeneration in a large family. JOURNAL Hum Mol Genet 12:3315-23 (2003) DOI:10.1093/hmg/ddg348 PMID:16998489 (CFHR1 CFHR3, reduced risk) AUTHORS Hughes AE, Orr N, Esfandiary H, Diaz-Torres M, Goodship T, Chakravarthy U TITLE A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration. JOURNAL Nat Genet 38:1173-7 (2006) DOI:10.1038/ng1890 PMID:9295268 (ABCA4) AUTHORS Allikmets R, Shroyer NF, Singh N, Seddon JM, Lewis RA, Bernstein PS, Peiffer A, Zabriskie NA, Li Y, Hutchinson A, Dean M, Lupski JR, Leppert M TITLE Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. JOURNAL Science 277:1805-7 (1997) DOI:10.1126/science.277.5333.1805 PMID:15269314 (FBLN5) AUTHORS Stone EM, Braun TA, Russell SR, Kuehn MH, Lotery AJ, Moore PA, Eastman CG, Casavant TL, Sheffield VC TITLE Missense variations in the fibulin 5 gene and age-related macular degeneration. JOURNAL N Engl J Med 351:346-53 (2004) DOI:10.1056/NEJMoa040833 PMID:15761122 (CFH) AUTHORS Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, Henning AK, SanGiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J TITLE Complement factor H polymorphism in age-related macular degeneration. JOURNAL Science 308:385-9 (2005) DOI:10.1126/science.1109557 PMID:16754848 (ERCC6) AUTHORS Tuo J, Ning B, Bojanowski CM, Lin ZN, Ross RJ, Reed GF, Shen D, Jiao X, Zhou M, Chew EY, Kadlubar FF, Chan CC TITLE Synergic effect of polymorphisms in ERCC6 5' flanking region and complement factor H on age-related macular degeneration predisposition. JOURNAL Proc Natl Acad Sci U S A 103:9256-61 (2006) DOI:10.1073/pnas.0603485103 PMID:15028672 (RAX2) AUTHORS Wang QL, Chen S, Esumi N, Swain PK, Haines HS, Peng G, Melia BM, McIntosh I, Heckenlively JR, Jacobson SG, Stone EM, Swaroop A, Zack DJ TITLE QRX, a novel homeobox gene, modulates photoreceptor gene expression. JOURNAL Hum Mol Genet 13:1025-40 (2004) DOI:10.1093/hmg/ddh117 PMID:17053108 (HTRA1) AUTHORS Dewan A, Liu M, Hartman S, Zhang SS, Liu DT, Zhao C, Tam PO, Chan WM, Lam DS, Snyder M, Barnstable C, Pang CP, Hoh J TITLE HTRA1 promoter polymorphism in wet age-related macular degeneration. JOURNAL Science 314:989-92 (2006) DOI:10.1126/science.1133807 PMID:16174643 (ARMS2) AUTHORS Rivera A, Fisher SA, Fritsche LG, Keilhauer CN, Lichtner P, Meitinger T, Weber BH TITLE Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk. JOURNAL Hum Mol Genet 14:3227-36 (2005) DOI:10.1093/hmg/ddi353 PMID:17634448 (C3) AUTHORS Yates JR, Sepp T, Matharu BK, Khan JC, Thurlby DA, Shahid H, Clayton DG, Hayward C, Morgan J, Wright AF, Armbrecht AM, Dhillon B, Deary IJ, Redmond E, Bird AC, Moore AT TITLE Complement C3 variant and the risk of age-related macular degeneration. JOURNAL N Engl J Med 357:553-61 (2007) DOI:10.1056/NEJMoa072618 PMID:15829498 (TLR4) AUTHORS Zareparsi S, Buraczynska M, Branham KE, Shah S, Eng D, Li M, Pawar H, Yashar BM, Moroi SE, Lichter PR, Petty HR, Richards JE, Abecasis GR, Elner VM, Swaroop A TITLE Toll-like receptor 4 variant D299G is associated with susceptibility to age-related macular degeneration. JOURNAL Hum Mol Genet 14:1449-55 (2005) DOI:10.1093/hmg/ddi154 PMID:11815350 (CST3) AUTHORS Zurdel J, Finckh U, Menzer G, Nitsch RM, Richard G TITLE CST3 genotype associated with exudative age related macular degeneration. JOURNAL Br J Ophthalmol 86:214-9 (2002) DOI:10.1136/bjo.86.2.214 PMID:15208270 (CX3CR1) AUTHORS Tuo J, Smith BC, Bojanowski CM, Meleth AD, Gery I, Csaky KG, Chew EY, Chan CC TITLE The involvement of sequence variation and expression of CX3CR1 in the pathogenesis of age-related macular degeneration. JOURNAL FASEB J 18:1297-9 (2004) DOI:10.1096/fj.04-1862fje PMID:23685748 (CFI) AUTHORS van de Ven JP, Nilsson SC, Tan PL, Buitendijk GH, Ristau T, Mohlin FC, Nabuurs SB, Schoenmaker-Koller FE, Smailhodzic D, Campochiaro PA, Zack DJ, Duvvari MR, Bakker B, Paun CC, Boon CJ, Uitterlinden AG, Liakopoulos S, Klevering BJ, Fauser S, Daha MR, Katsanis N, Klaver CC, Blom AM, Hoyng CB, den Hollander AI TITLE A functional variant in the CFI gene confers a high risk of age-related macular degeneration. JOURNAL Nat Genet 45:813-7 (2013) DOI:10.1038/ng.2640 PMID:16518403 (C2 CFB) AUTHORS Gold B, Merriam JE, Zernant J, Hancox LS, Taiber AJ, Gehrs K, Cramer K, Neel J, Bergeron J, Barile GR, Smith RT, Hageman GS, Dean M, Allikmets R TITLE Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. JOURNAL Nat Genet 38:458-62 (2006) DOI:10.1038/ng1750 PMID:24036952 (C9) AUTHORS Seddon JM, Yu Y, Miller EC, Reynolds R, Tan PL, Gowrisankar S, Goldstein JI, Triebwasser M, Anderson HE, Zerbib J, Kavanagh D, Souied E, Katsanis N, Daly MJ, Atkinson JP, Raychaudhuri S TITLE Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration. JOURNAL Nat Genet 45:1366-70 (2013) DOI:10.1038/ng.2741 |