Skip to main content
SpringerLink
Log in

Genetics of Age-Related Macular Degeneration in Asia

  • Chapter
  • First Online:
Advances in Vision Research, Volume III

Part of the book series: Essentials in Ophthalmology ((ESSENTIALS))

  • 418 Accesses

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness among elderly people in Western countries. Recently, the prevalence of AMD has also increased in Asia. Although the precise mechanisms of AMD development have not been thoroughly elucidated, both environmental and genetic factors are thought to contribute to its development. As for environmental factors, aging and smoking are the two major risk factors for developing AMD. More than 30 genes associated with AMD have been discovered through genome-wide association studies (GWASs). In addition to their association with the disease development, susceptibility genes for AMD can predict the lesion size and bilaterality of AMD, and genetic information might be useful to conduct personalized medicine for AMD. Recently, the concept of pachychoroid spectrum disease has been introduced, and studies have begun to clarify the genetic architecture of pachychoroid disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Allikmets R, Singh N, Sun H, et al. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat Genet. 1997;15(3):236–46.

    Article  CAS  PubMed  Google Scholar 

  2. Zhang K, Kniazeva M, Han M, et al. A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy. Nat Genet. 2001;27(1):89–93.

    Article  CAS  PubMed  Google Scholar 

  3. Weber BH, Vogt G, Pruett RC, Stohr H, Felbor U. Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby’s fundus dystrophy. Nat Genet. 1994;8(4):352–6.

    Article  CAS  PubMed  Google Scholar 

  4. Stone EM, Lotery AJ, Munier FL, et al. A single EFEMP1 mutation associated with both Malattia Leventinese and Doyne honeycomb retinal dystrophy. Nat Genet. 1999;22(2):199–202.

    Article  CAS  PubMed  Google Scholar 

  5. Petrukhin K, Koisti MJ, Bakall B, et al. Identification of the gene responsible for Best macular dystrophy. Nat Genet. 1998;19(3):241–7.

    Article  CAS  PubMed  Google Scholar 

  6. Marquardt A, Stohr H, Passmore LA, Kramer F, Rivera A, Weber BH. Mutations in a novel gene, VMD2, encoding a protein of unknown properties cause juvenile-onset vitelliform macular dystrophy (Best’s disease). Hum Mol Genet. 1998;7(9):1517–25.

    Article  CAS  PubMed  Google Scholar 

  7. Allikmets R, Shroyer NF, Singh N, et al. Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science. 1997;277(5333):1805–7.

    Article  CAS  PubMed  Google Scholar 

  8. Kuroiwa S, Kojima H, Kikuchi T, Yoshimura N. ATP binding cassette transporter retina genotypes and age related macular degeneration: an analysis on exudative non-familial Japanese patients. Br J Ophthalmol. 1999;83(5):613–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Fuse N, Suzuki T, Wada Y, et al. Molecular genetic analysis of ABCR gene in Japanese dry form age-related macular degeneration. Jpn J Ophthalmol. 2000;44(3):245–9.

    Article  CAS  PubMed  Google Scholar 

  10. Allikmets R. Further evidence for an association of ABCR alleles with age-related macular degeneration. The international ABCR screening consortium. Am J Hum Genet. 2000;67(2):487–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. De La Paz MA, Guy VK, Abou-Donia S, et al. Analysis of the Stargardt disease gene (ABCR) in age-related macular degeneration. Ophthalmology. 1999;106(8):1531–6.

    Article  Google Scholar 

  12. Rivera A, White K, Stohr H, et al. A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration. Am J Hum Genet. 2000;67(4):800–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Souied EH, Ducroq D, Rozet JM, et al. ABCR gene analysis in familial exudative age-related macular degeneration. Invest Ophthalmol Vis Sci. 2000;41(1):244–7.

    CAS  PubMed  Google Scholar 

  14. Guymer RH, Heon E, Lotery AJ, et al. Variation of codons 1961 and 2177 of the Stargardt disease gene is not associated with age-related macular degeneration. Arch Ophthalmol. 2001;119(5):745–51.

    Article  CAS  PubMed  Google Scholar 

  15. Schmidt S, Postel EA, Agarwal A, et al. Detailed analysis of allelic variation in the ABCA4 gene in age-related maculopathy. Invest Ophthalmol Vis Sci. 2003;44(7):2868–75.

    Article  PubMed  Google Scholar 

  16. Felbor U, Doepner D, Schneider U, Zrenner E, Weber BH. Evaluation of the gene encoding the tissue inhibitor of metalloproteinases-3 in various maculopathies. Invest Ophthalmol Vis Sci. 1997;38(6):1054–9.

    CAS  PubMed  Google Scholar 

  17. De La Paz MA, Pericak-Vance MA, Lennon F, Haines JL, Seddon JM. Exclusion of TIMP3 as a candidate locus in age-related macular degeneration. Invest Ophthalmol Vis Sci. 1997;38(6):1060–5.

    Google Scholar 

  18. Allikmets R, Seddon JM, Bernstein PS, et al. Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies. Hum Genet. 1999;104(6):449–53.

    Article  CAS  PubMed  Google Scholar 

  19. Lotery AJ, Munier FL, Fishman GA, et al. Allelic variation in the VMD2 gene in best disease and age-related macular degeneration. Invest Ophthalmol Vis Sci. 2000;41(6):1291–6.

    CAS  PubMed  Google Scholar 

  20. Kramer F, White K, Pauleikhoff D, et al. Mutations in the VMD2 gene are associated with juvenile-onset vitelliform macular dystrophy (Best disease) and adult vitelliform macular dystrophy but not age-related macular degeneration. Eur J Hum Genet. 2000;8(4):286–92.

    Article  CAS  PubMed  Google Scholar 

  21. Ayyagari R, Zhang K, Hutchinson A, et al. Evaluation of the ELOVL4 gene in patients with age-related macular degeneration. Ophthalmic Genet. 2001;22(4):233–9.

    Article  CAS  PubMed  Google Scholar 

  22. Conley YP, Thalamuthu A, Jakobsdottir J, et al. Candidate gene analysis suggests a role for fatty acid biosynthesis and regulation of the complement system in the etiology of age-related maculopathy. Hum Mol Genet. 2005;14(14):1991–2002.

    Article  CAS  PubMed  Google Scholar 

  23. Seitsonen S, Lemmela S, Holopainen J, et al. Analysis of variants in the complement factor H, the elongation of very long chain fatty acids-like 4 and the hemicentin 1 genes of age-related macular degeneration in the Finnish population. Mol Vis. 2006;12:796–801.

    Google Scholar 

  24. DeAngelis MM, Ji F, Kim IK, et al. Cigarette smoking, CFH, APOE, ELOVL4, and risk of neovascular age-related macular degeneration. Arch Ophthalmol. 2007;125(1):49–54.

    Article  CAS  PubMed  Google Scholar 

  25. Fritsche LG, Chen W, Schu M, et al. Seven new loci associated with age-related macular degeneration. Nat Genet. 2013;45(4):433–9. 439e431-432

    Article  CAS  PubMed  Google Scholar 

  26. Klein ML, Schultz DW, Edwards A, et al. Age-related macular degeneration. Clinical features in a large family and linkage to chromosome 1q. Arch Ophthalmol. 1998;116(8):1082–8.

    Article  CAS  PubMed  Google Scholar 

  27. Weeks DE, Conley YP, Tsai HJ, et al. Age-related maculopathy: an expanded genome-wide scan with evidence of susceptibility loci within the 1q31 and 17q25 regions. Am J Ophthalmol. 2001;132(5):682–92.

    Article  CAS  PubMed  Google Scholar 

  28. Schultz DW, Klein ML, Humpert AJ, et al. Analysis of the ARMD1 locus: evidence that a mutation in HEMICENTIN-1 is associated with age-related macular degeneration in a large family. Hum Mol Genet. 2003;12(24):3315–23.

    Article  CAS  PubMed  Google Scholar 

  29. Abecasis GR, Yashar BM, Zhao Y, et al. Age-related macular degeneration: a high-resolution genome scan for susceptibility loci in a population enriched for late-stage disease. Am J Hum Genet. 2004;74(3):482–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bojanowski CM, Tuo J, Chew EY, Csaky KG, Chan CC. Analysis of hemicentin-1, hOgg1, and E-selectin single nucleotide polymorphisms in age-related macular degeneration. Trans Am Ophthalmol Soc. 2005;103:37–44; discussion 44-35.

    Google Scholar 

  31. Fuse N, Miyazawa A, Mengkegale M, et al. Polymorphisms in complement factor H and hemicentin-1 genes in a Japanese population with dry-type age-related macular degeneration. Am J Ophthalmol. 2006;142(6):1074–6.

    Article  CAS  PubMed  Google Scholar 

  32. Fisher SA, Rivera A, Fritsche LG, et al. Case-control genetic association study of fibulin-6 (FBLN6 or HMCN1) variants in age-related macular degeneration (AMD). Hum Mutat. 2007;28(4):406–13.

    Article  CAS  PubMed  Google Scholar 

  33. Strittmatter WJ, Saunders AM, Schmechel D, et al. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA. 1993;90(5):1977–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Saunders AM, Strittmatter WJ, Schmechel D, et al. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease. Neurology. 1993;43(8):1467–72.

    Article  CAS  PubMed  Google Scholar 

  35. Klaver CC, Kliffen M, van Duijn CM, et al. Genetic association of apolipoprotein E with age-related macular degeneration. Am J Hum Genet. 1998;63(1):200–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Xiying M, Wenbo W, Wangyi F, Qinghuai L. Association of apolipoprotein E polymorphisms with age-related macular degeneration subtypes: an updated systematic review and meta-analysis. Arch Med Res. 2017;48(4):370–7.

    Article  PubMed  CAS  Google Scholar 

  37. Kimura K, Isashiki Y, Sonoda S, Kakiuchi-Matsumoto T, Ohba N. Genetic association of manganese superoxide dismutase with exudative age-related macular degeneration. Am J Ophthalmol. 2000;130(6):769–73.

    Article  CAS  PubMed  Google Scholar 

  38. Gotoh N, Yamada R, Matsuda F, Yoshimura N, Iida T. Manganese superoxide dismutase gene (SOD2) polymorphism and exudative age-related macular degeneration in the Japanese population. Am J Ophthalmol. 2008;146(1):146.

    Article  CAS  PubMed  Google Scholar 

  39. Esfandiary H, Chakravarthy U, Patterson C, Young I, Hughes AE. Association study of detoxification genes in age related macular degeneration. Br J Ophthalmol. 2005;89(4):470–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Brion M, Sanchez-Salorio M, Corton M, et al. Genetic association study of age-related macular degeneration in the Spanish population. Acta Ophthalmol. 2011;89(1):e12–22.

    Article  PubMed  Google Scholar 

  41. Ikeda T, Obayashi H, Hasegawa G, et al. Paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level as possible risk factors for exudative age-related macular degeneration. Am J Ophthalmol. 2001;132(2):191–5.

    Article  CAS  PubMed  Google Scholar 

  42. Baird PN, Chu D, Guida E, Vu HT, Guymer R. Association of the M55L and Q192R paraoxonase gene polymorphisms with age-related macular degeneration. Am J Ophthalmol. 2004;138(4):665–6.

    Article  CAS  PubMed  Google Scholar 

  43. Pauer GJ, Sturgill GM, Peachey NS, Hagstrom SA. Protective effect of paraoxonase 1 gene variant Gln192Arg in age-related macular degeneration. Am J Ophthalmol. 2010;149(3):513–22.

    Article  CAS  PubMed  Google Scholar 

  44. Sogut E, Ortak H, Aydogan L, Benli I. Association of paraoxonase 1 L55M and Q192R single-nucleotide polymorphisms with age-related macular degeneration. Retina. 2013;33(9):1836–42.

    Article  PubMed  CAS  Google Scholar 

  45. Haines JL, Schnetz-Boutaud N, Schmidt S, et al. Functional candidate genes in age-related macular degeneration: significant association with VEGF, VLDLR, and LRP6. Invest Ophthalmol Vis Sci. 2006;47(1):329–35.

    Article  PubMed  Google Scholar 

  46. Churchill AJ, Carter JG, Lovell HC, et al. VEGF polymorphisms are associated with neovascular age-related macular degeneration. Hum Mol Genet. 2006;15(19):2955–61.

    Article  CAS  PubMed  Google Scholar 

  47. Lin JM, Wan L, Tsai YY, et al. Vascular endothelial growth factor gene polymorphisms in age-related macular degeneration. Am J Ophthalmol. 2008;145(6):1045–51.

    Article  CAS  PubMed  Google Scholar 

  48. Yamagishi S, Nakamura K, Inoue H, Takeuchi M. Met72Thr polymorphism of pigment epithelium-derived factor gene and susceptibility to age-related macular degeneration. Med Hypotheses. 2005;64(6):1202–4.

    Article  CAS  PubMed  Google Scholar 

  49. Lin JM, Wan L, Tsai YY, et al. Pigment epithelium-derived factor gene Met72Thr polymorphism is associated with increased risk of wet age-related macular degeneration. Am J Ophthalmol. 2008;145(4):716–21.

    Article  CAS  PubMed  Google Scholar 

  50. Mattes D, Haas A, Renner W, et al. Analysis of three pigment epithelium-derived factor gene polymorphisms in patients with exudative age-related macular degeneration. Mol Vis. 2009;15:343–8.

    Google Scholar 

  51. Mori K, Horie-Inoue K, Gehlbach PL, et al. Phenotype and genotype characteristics of age-related macular degeneration in a Japanese population. Ophthalmology. 2010;117(5):928–38.

    Article  PubMed  Google Scholar 

  52. Qu Y, Zhang X, Dai H, et al. Pigment epithelium-derived factor gene polymorphisms in exudative age-related degeneration in a Chinese cohort. Curr Eye Res. 2011;36(1):60–5.

    Article  CAS  PubMed  Google Scholar 

  53. Wu K, Wen F, Zuo C, et al. Lack of association with PEDF Met72Thr variant in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a Han Chinese population. Curr Eye Res. 2012;37(1):68–72.

    Article  CAS  PubMed  Google Scholar 

  54. Ma L, Tang SM, Rong SS, et al. Association of PEDF polymorphisms with age-related macular degeneration and polypoidal choroidal vasculopathy: a systematic review and meta-analysis. Sci Rep. 2015;5:9497.

    Google Scholar 

  55. Klein RJ, Zeiss C, Chew EY, et al. Complement factor H polymorphism in age-related macular degeneration. Science. 2005;308(5720):385–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Haines JL, Hauser MA, Schmidt S, et al. Complement factor H variant increases the risk of age-related macular degeneration. Science. 2005;308(5720):419–21.

    Article  CAS  PubMed  Google Scholar 

  57. Edwards AO, Ritter R 3rd, Abel KJ, Manning A, Panhuysen C, Farrer LA. Complement factor H polymorphism and age-related macular degeneration. Science. 2005;308(5720):421–4.

    Article  CAS  PubMed  Google Scholar 

  58. Gotoh N, Yamada R, Hiratani H, et al. No association between complement factor H gene polymorphism and exudative age-related macular degeneration in Japanese. Hum Genet. 2006;120(1):139–43.

    Article  CAS  PubMed  Google Scholar 

  59. Uka J, Tamura H, Kobayashi T, et al. No association of complement factor H gene polymorphism and age-related macular degeneration in the Japanese population. Retina. 2006;26(9):985–7.

    Article  PubMed  Google Scholar 

  60. Okamoto H, Umeda S, Obazawa M, et al. Complement factor H polymorphisms in Japanese population with age-related macular degeneration. Mol Vis. 2006;12:156–8.

    Google Scholar 

  61. Mori K, Gehlbach PL, Kabasawa S, et al. Coding and noncoding variants in the CFH gene and cigarette smoking influence the risk of age-related macular degeneration in a Japanese population. Invest Ophthalmol Vis Sci. 2007;48(11):5315–9.

    Article  PubMed  Google Scholar 

  62. Kim NR, Kang JH, Kwon OW, Lee SJ, Oh JH, Chin HS. Association between complement factor H gene polymorphisms and neovascular age-related macular degeneration in Koreans. Invest Ophthalmol Vis Sci. 2008;49(5):2071–6.

    Article  PubMed  Google Scholar 

  63. Chen LJ, Liu DT, Tam PO, et al. Association of complement factor H polymorphisms with exudative age-related macular degeneration. Mol Vis. 2006;12:1536–42.

    Google Scholar 

  64. Ng TK, Chen LJ, Liu DT, et al. Multiple gene polymorphisms in the complement factor h gene are associated with exudative age-related macular degeneration in Chinese. Invest Ophthalmol Vis Sci. 2008;49(8):3312–7.

    Article  PubMed  Google Scholar 

  65. Hayashi H, Yamashiro K, Gotoh N, et al. CFH and ARMS2 variations in age-related macular degeneration, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation. Invest Ophthalmol Vis Sci. 2010;51(11):5914–9.

    Article  PubMed  Google Scholar 

  66. Kondo N, Bessho H, Honda S, Negi A. Complement factor H Y402H variant and risk of age-related macular degeneration in Asians: a systematic review and meta-analysis. Ophthalmology. 2011;118(2):339–44.

    Article  PubMed  Google Scholar 

  67. Jakobsdottir J, Conley YP, Weeks DE, Mah TS, Ferrell RE, Gorin MB. Susceptibility genes for age-related maculopathy on chromosome 10q26. Am J Hum Genet. 2005;77(3):389–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Dewan A, Liu M, Hartman S, et al. HTRA1 promoter polymorphism in wet age-related macular degeneration. Science. 2006;314(5801):989–92.

    Article  CAS  PubMed  Google Scholar 

  69. Yang Z, Camp NJ, Sun H, et al. A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science. 2006;314(5801):992–3.

    Article  CAS  PubMed  Google Scholar 

  70. Rivera A, Fisher SA, Fritsche LG, et al. Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk. Hum Mol Genet. 2005;14(21):3227–36.

    Article  CAS  PubMed  Google Scholar 

  71. Neale BM, Fagerness J, Reynolds R, et al. Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC). Proc Natl Acad Sci USA. 2010;107(16):7395–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Chen W, Stambolian D, Edwards AO, et al. Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. Proc Natl Acad Sci USA. 2010;107(16):7401–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Fritsche LG, Igl W, Bailey JN, et al. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat Genet. 2016;48(2):134–43.

    Article  CAS  PubMed  Google Scholar 

  74. Arakawa S, Takahashi A, Ashikawa K, et al. Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population. Nat Genet. 2011;43(10):1001–4.

    Article  CAS  PubMed  Google Scholar 

  75. Nakata I, Yamashiro K, Akagi-Kurashige Y, et al. Association of genetic variants on 8p21 and 4q12 with age-related macular degeneration in Asian populations. Invest Ophthalmol Vis Sci. 2012;53(10):6576–81.

    Article  CAS  PubMed  Google Scholar 

  76. Cheng CY, Yamashiro K, Chen LJ, et al. New loci and coding variants confer risk for age-related macular degeneration in East Asians. Nat Commun. 2015;6:6063.

    Google Scholar 

  77. Huang L, Zhang H, Cheng CY, et al. A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy. Nat Genet. 2016;48(6):640–7.

    Article  CAS  PubMed  Google Scholar 

  78. Gold B, Merriam JE, Zernant J, et al. Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nat Genet. 2006;38(4):458–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Maller JB, Fagerness JA, Reynolds RC, Neale BM, Daly MJ, Seddon JM. Variation in complement factor 3 is associated with risk of age-related macular degeneration. Nat Genet. 2007;39(10):1200–1.

    Article  CAS  PubMed  Google Scholar 

  80. Yates JR, Sepp T, Matharu BK, et al. Complement C3 variant and the risk of age-related macular degeneration. N Engl J Med. 2007;357(6):553–61.

    Article  CAS  PubMed  Google Scholar 

  81. Fagerness JA, Maller JB, Neale BM, Reynolds RC, Daly MJ, Seddon JM. Variation near complement factor I is associated with risk of advanced AMD. Eur J Hum Genet. 2009;17(1):100–4.

    Article  CAS  PubMed  Google Scholar 

  82. Ennis S, Jomary C, Mullins R, et al. Association between the SERPING1 gene and age-related macular degeneration: a two-stage case-control study. Lancet. 2008;372(9652):1828–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Allikmets R, Dean M, Hageman GS, et al. The SERPING1 gene and age-related macular degeneration. Lancet. 2009;374(9693):875–6.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Park KH, Ryu E, Tosakulwong N, Wu Y, Edwards AO. Common variation in the SERPING1 gene is not associated with age-related macular degeneration in two independent groups of subjects. Mol Vis. 2009;15:200–7.

    Google Scholar 

  85. Nakata I, Yamashiro K, Yamada R, et al. Association between the SERPING1 gene and age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese. PLoS One. 2011;6(4):e19108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Liu K, Lai TY, Ma L, et al. Ethnic differences in the association of SERPING1 with age-related macular degeneration and polypoidal choroidal vasculopathy. Sci Rep. 2015;5:9424.

    Google Scholar 

  87. Fan Q, Cheung CMG, Chen LJ, et al. Shared genetic variants for polypoidal choroidal vasculopathy and typical neovascular age-related macular degeneration in East Asians. J Hum Genet. 2017;62(12):1049–55.

    Article  PubMed  Google Scholar 

  88. Seddon JM, Yu Y, Miller EC, et al. Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration. Nat Genet. 2013;45(11):1366–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Yu Y, Bhangale TR, Fagerness J, et al. Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration. Hum Mol Genet. 2011;20(18):3699–709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Zhang X, Li M, Wen F, et al. Different impact of high-density lipoprotein-related genetic variants on polypoidal choroidal vasculopathy and neovascular age-related macular degeneration in a Chinese Han population. Exp Eye Res. 2013;108:16–22.

    Google Scholar 

  91. Zhou J, Wang D, Zhang J, et al. RAD51 gene is associated with advanced age-related macular degeneration in Chinese population. Clin Biochem. 2013;46(16–17):1689–93.

    Article  CAS  PubMed  Google Scholar 

  92. Yanagisawa S, Kondo N, Miki A, et al. A common complement C3 variant is associated with protection against wet age-related macular degeneration in a Japanese population. PLoS One. 2011;6(12):e28847.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Pei XT, Li XX, Bao YZ, et al. Association of c3 gene polymorphisms with neovascular age-related macular degeneration in a chinese population. Curr Eye Res. 2009;34(8):615–22.

    Article  CAS  PubMed  Google Scholar 

  94. McKay GJ, Patterson CC, Chakravarthy U, et al. Evidence of association of APOE with age-related macular degeneration: a pooled analysis of 15 studies. Hum Mutat. 2011;32(12):1407–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Kanda A, Chen W, Othman M, et al. A variant of mitochondrial protein LOC387715/ARMS2, not HTRA1, is strongly associated with age-related macular degeneration. Proc Natl Acad Sci USA. 2007;104(41):16227–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Fritsche LG, Loenhardt T, Janssen A, et al. Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA. Nat Genet. 2008;40(7):892–6.

    Article  CAS  PubMed  Google Scholar 

  97. Kortvely E, Hauck SM, Duetsch G, et al. ARMS2 is a constituent of the extracellular matrix providing a link between familial and sporadic age-related macular degenerations. Invest Ophthalmol Vis Sci. 2010;51(1):79–88.

    Article  PubMed  Google Scholar 

  98. Wang G, Spencer KL, Scott WK, et al. Analysis of the indel at the ARMS2 3’UTR in age-related macular degeneration. Hum Genet. 2010;127(5):595–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Micklisch S, Lin Y, Jacob S, et al. Age-related macular degeneration associated polymorphism rs10490924 in ARMS2 results in deficiency of a complement activator. J Neuroinflammation. 2017;14(1):4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Vierkotten S, Muether PS, Fauser S. Overexpression of HTRA1 leads to ultrastructural changes in the elastic layer of Bruch’s membrane via cleavage of extracellular matrix components. PLoS One. 2011;6(8):e22959.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Jones A, Kumar S, Zhang N, et al. Increased expression of multifunctional serine protease, HTRA1, in retinal pigment epithelium induces polypoidal choroidal vasculopathy in mice. Proc Natl Acad Sci USA. 2011;108(35):14578–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Kondo N, Honda S, Ishibashi K, Tsukahara Y, Negi A. Elastin gene polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Invest Ophthalmol Vis Sci. 2008;49(3):1101–5.

    Article  PubMed  Google Scholar 

  103. Yamashiro K, Mori K, Nakata I, et al. Association of elastin gene polymorphism to age-related macular degeneration and polypoidal choroidal vasculopathy. Invest Ophthalmol Vis Sci. 2011;52(12):8780–4.

    Article  CAS  PubMed  Google Scholar 

  104. Tanaka K, Nakayama T, Yuzawa M, et al. Analysis of candidate genes for age-related macular degeneration subtypes in the Japanese population. Mol Vis. 2011;17:2751–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Bessho H, Honda S, Kondo N, Kusuhara S, Tsukahara Y, Negi A. The association of CD36 variants with polypoidal choroidal vasculopathy compared to typical neovascular age-related macular degeneration. Mol Vis. 2012;18:121–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Yang Z, Stratton C, Francis PJ, et al. Toll-like receptor 3 and geographic atrophy in age-related macular degeneration. N Engl J Med. 2008;359(14):1456–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Allikmets R, Bergen AA, Dean M, et al. Geographic atrophy in age-related macular degeneration and TLR3. N Engl J Med. 2009;360(21):2252–4. author reply 2255-2256

    CAS  PubMed  Google Scholar 

  108. Cho Y, Wang JJ, Chew EY, et al. Toll-like receptor polymorphisms and age-related macular degeneration: replication in three case-control samples. Invest Ophthalmol Vis Sci. 2009;50(12):5614–8.

    Article  PubMed  Google Scholar 

  109. Ma L, Tang FY, Chu WK, et al. Association of toll-like receptor 3 polymorphism rs3775291 with age-related macular degeneration: a systematic review and meta-analysis. Sci Rep. 2016;6:19718.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Seddon JM, Francis PJ, George S, Schultz DW, Rosner B, Klein ML. Association of CFH Y402H and LOC387715 A69S with progression of age-related macular degeneration. JAMA. 2007;297(16):1793–800.

    Article  CAS  PubMed  Google Scholar 

  111. Seddon JM, Reynolds R, Maller J, Fagerness JA, Daly MJ, Rosner B. Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables. Invest Ophthalmol Vis Sci. 2009;50(5):2044–53.

    Article  PubMed  Google Scholar 

  112. Gotoh N, Yamada R, Nakanishi H, et al. Correlation between CFH Y402H and HTRA1 rs11200638 genotype to typical exudative age-related macular degeneration and polypoidal choroidal vasculopathy phenotype in the Japanese population. Clin Exp Ophthalmol. 2008;36(5):437–42.

    PubMed  Google Scholar 

  113. Sakurada Y, Kubota T, Imasawa M, et al. Role of complement factor H I62V and age-related maculopathy susceptibility 2 A69S variants in the clinical expression of polypoidal choroidal vasculopathy. Ophthalmology. 2011;118(7):1402–7.

    PubMed  Google Scholar 

  114. Kawashima-Kumagai K, Yamashiro K, Yoshikawa M, et al. A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration. Sci Rep. 2017;7(1):7173.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Tamura H, Tsujikawa A, Yamashiro K, et al. Association of ARMS2 genotype with bilateral involvement of exudative age-related macular degeneration. Am J Ophthalmol. 2012;154(3):542–8. e541

    Article  CAS  PubMed  Google Scholar 

  116. Miyake M, Yamashiro K, Tamura H, et al. The contribution of genetic architecture to the 10-year incidence of age-related macular degeneration in the fellow eye. Invest Ophthalmol Vis Sci. 2015;56(9):5353–61.

    Article  PubMed  Google Scholar 

  117. Maguire MG, Daniel E, Shah AR, et al. Incidence of choroidal neovascularization in the fellow eye in the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2013;120(10):2035–41.

    Article  PubMed  Google Scholar 

  118. Brantley MA Jr, Fang AM, King JM, Tewari A, Kymes SM, Shiels A. Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to intravitreal bevacizumab. Ophthalmology. 2007;114(12):2168–73.

    Article  PubMed  Google Scholar 

  119. Bessho H, Honda S, Kondo N, Negi A. The association of age-related maculopathy susceptibility 2 polymorphisms with phenotype in typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Mol Vis. 2011;17:977–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Akagi-Kurashige Y, Yamashiro K, Gotoh N, et al. MMP20 and ARMS2/HTRA1 are associated with neovascular lesion size in age-related macular degeneration. Ophthalmology. 2015;122(11):2295–302. e2292

    Article  PubMed  Google Scholar 

  121. Sakurada Y, Kubota T, Mabuchi F, Imasawa M, Tanabe N, Iijima H. Association of LOC387715 A69S with vitreous hemorrhage in polypoidal choroidal vasculopathy. Am J Ophthalmol. 2008;145(6):1058–62.

    Article  CAS  PubMed  Google Scholar 

  122. Sakurada Y, Kubota T, Imasawa M, Mabuchi F, Tanabe N, Iijima H. Association of LOC387715 A69S genotype with visual prognosis after photodynamic therapy for polypoidal choroidal vasculopathy. Retina. 2010;30(10):1616–21.

    Article  PubMed  Google Scholar 

  123. Tsuchihashi T, Mori K, Horie-Inoue K, et al. Complement factor H and high-temperature requirement A-1 genotypes and treatment response of age-related macular degeneration. Ophthalmology. 2011;118(1):93–100.

    Article  PubMed  Google Scholar 

  124. Chowers I, Meir T, Lederman M, et al. Sequence variants in HTRA1 and LOC387715/ARMS2 and phenotype and response to photodynamic therapy in neovascular age-related macular degeneration in populations from Israel. Mol Vis. 2008;14:2263–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Brantley MA Jr, Edelstein SL, King JM, et al. Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to photodynamic therapy. Eye (Lond). 2009;23(3):626–31.

    Article  CAS  Google Scholar 

  126. Yamashiro K, Tomita K, Tsujikawa A, et al. Factors associated with the response of age-related macular degeneration to intravitreal ranibizumab treatment. Am J Ophthalmol. 2012;154(1):125–36.

    Article  CAS  PubMed  Google Scholar 

  127. Hata M, Tsujikawa A, Miyake M, et al. Two-year visual outcome of ranibizumab in typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Graefes Arch Clin Exp Ophthalmol. 2015;253(2):221–7.

    Article  PubMed  Google Scholar 

  128. Kang HK, Yoon MH, Lee DH, Chin HS. Pharmacogenetic influence of LOC387715/HTRA1 on the efficacy of bevacizumab treatment for age-related macular degeneration in a Korean population. Korean J Ophthalmol. 2012;26(6):414–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Yuan D, Liu X, Yuan S, Xie P, Liu Q. Genetic association with response to intravitreal ranibizumab for neovascular age-related macular degeneration in the Han Chinese population. Ophthalmologica. 2013;230(4):227–32.

    Article  CAS  PubMed  Google Scholar 

  130. Chang W, Noh DH, Sagong M, Kim IT. Pharmacogenetic association with early response to intravitreal ranibizumab for age-related macular degeneration in a Korean population. Mol Vis. 2013;19:702–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Park UC, Shin JY, Kim SJ, et al. Genetic factors associated with response to intravitreal ranibizumab in Korean patients with neovascular age-related macular degeneration. Retina. 2014;34(2):288–97.

    Article  CAS  PubMed  Google Scholar 

  132. Hagstrom SA, Ying GS, Pauer GJT, et al. Pharmacogenetics for genes associated with age-related macular degeneration in the comparison of AMD treatments trials (CATT). Ophthalmology. 2013;120(3):593–9.

    Article  PubMed  Google Scholar 

  133. Teper SJ, Nowinska A, Pilat J, Palucha A, Wylegala E. Involvement of genetic factors in the response to a variable-dosing ranibizumab treatment regimen for age-related macular degeneration. Mol Vis. 2010;16:2598–604.

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Abedi F, Wickremasinghe S, Richardson AJ, Islam AF, Guymer RH, Baird PN. Genetic influences on the outcome of anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration. Ophthalmology. 2013;120(8):1641–8.

    Article  PubMed  Google Scholar 

  135. Tian J, Qin X, Fang K, et al. Association of genetic polymorphisms with response to bevacizumab for neovascular age-related macular degeneration in the Chinese population. Pharmacogenomics. 2012;13(7):779–87.

    Article  CAS  PubMed  Google Scholar 

  136. Yamashiro K, Mori K, Honda S, et al. A prospective multicenter study on genome wide associations to ranibizumab treatment outcome for age-related macular degeneration. Sci Rep. 2017;7(1):9196.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Warrow DJ, Hoang QV, Freund KB. Pachychoroid pigment epitheliopathy. Retina. 2013;33(8):1659–72.

    Article  PubMed  Google Scholar 

  138. Takahashi A, Ooto S, Yamashiro K, et al. Pachychoroid geographic atrophy: clinical and genetic characteristics. Ophthalmol Retina. 2018;2(4):295–305.

    Article  PubMed  Google Scholar 

  139. Pang CE, Freund KB. Pachychoroid neovasculopathy. Retina. 2015;35(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  140. Hosoda Y, Yoshikawa M, Miyake M, et al. CFH and VIPR2 as susceptibility loci in choroidal thickness and pachychoroid disease central serous chorioretinopathy. Proc Natl Acad Sci USA. 2018;115(24):6261–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Dansingani KK, Perlee LT, Hamon S, et al. Risk alleles associated with neovascularization in a pachychoroid phenotype. Ophthalmology. 2016;123(12):2628–30.

    Article  PubMed  Google Scholar 

  142. Miyake M, Ooto S, Yamashiro K, et al. Pachychoroid neovasculopathy and age-related macular degeneration. Sci Rep. 2015;5:16204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Otsu Red Cross Hospital, Otsu, Japan

    Kenji Yamashiro

Authors
  1. Kenji Yamashiro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenji Yamashiro .

Editor information

Editors and Affiliations

  1. National Eye Institute, National Institutes of Health, Bethesda, MD, USA

    Gyan Prakash

  2. National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan

    Takeshi Iwata

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Yamashiro, K. (2021). Genetics of Age-Related Macular Degeneration in Asia. In: Prakash, G., Iwata, T. (eds) Advances in Vision Research, Volume III. Essentials in Ophthalmology. Springer, Singapore. https://doi.org/10.1007/978-981-15-9184-6_6

Download citation

  • DOI: https://doi.org/10.1007/978-981-15-9184-6_6

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-15-9183-9

  • Online ISBN: 978-981-15-9184-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation