The Hypothetical Molecular Mechanism of the Ethnic Variations in the Manifestation of Age-related Macular Degeneration; Focuses on the Functions of the Most Significant Susceptibility Genes

Overview

Journal Graefes Arch Clin Exp Ophthalmol

Specialty Ophthalmology

Date 2024 Mar 20

PMID 38507046

Authors

Shigeru Honda

Norihiko Misawa

Yusuke Sato

Daisuke Oikawa

Fuminori Tokunaga

Affiliations

Soon will be listed here.

Abstract

Age-related macular degeneration (AMD) is the leading sight-threatening disease in developed countries. On the other hand, recent studies indicated an ethnic variation in the phenotype of AMD. For example, several reports demonstrated that the incidence of drusen in AMD patients is less in Asians compared to Caucasians though the reason has not been clarified yet. In the last decades, several genome association studies have disclosed many susceptible genes of AMD and revealed that the association strength of some genes was different among races and AMD phenotypes. In this review article, the essential findings of the clinical studies and genome association studies for the most significant genes CFH and ARMS2/HTRA1 in AMD of different races are summarized, and theoretical hypotheses about the molecular mechanisms underlying the ethnic variation in the AMD manifestation mainly focused on those genes between Caucasians and Asians are discussed.

Citing Articles

Drusen in AMD from the Perspective of Cholesterol Metabolism and Hypoxic Response.

Ban N, Shinojima A, Negishi K, Kurihara T J Clin Med. 2024; 13(9).

PMID: 38731137 PMC: 11084323. DOI: 10.3390/jcm13092608.

References

Klein R, Klein B, Knudtson M, Meuer S, Swift M, Gangnon R . Fifteen-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study. Ophthalmology. 2007; 114(2):253-62. DOI: 10.1016/j.ophtha.2006.10.040. View

Wong W, Su X, Li X, Cheung C, Klein R, Cheng C . Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014; 2(2):e106-16. DOI: 10.1016/S2214-109X(13)70145-1. View

Abdelsalam A, Del Priore L, Zarbin M . Drusen in age-related macular degeneration: pathogenesis, natural course, and laser photocoagulation-induced regression. Surv Ophthalmol. 1999; 44(1):1-29. DOI: 10.1016/s0039-6257(99)00072-7. View

Ferris F, Davis M, Clemons T, Lee L, Chew E, Lindblad A . A simplified severity scale for age-related macular degeneration: AREDS Report No. 18. Arch Ophthalmol. 2005; 123(11):1570-4. PMC: 1473206. DOI: 10.1001/archopht.123.11.1570. View

Yannuzzi L, Negrao S, Iida T, Carvalho C, Slakter J, Freund K . Retinal angiomatous proliferation in age-related macular degeneration. Retina. 2001; 21(5):416-34. DOI: 10.1097/00006982-200110000-00003. View

Sho K, Takahashi K, Yamada H, Wada M, Nagai Y, Otsuji T . Polypoidal choroidal vasculopathy: incidence, demographic features, and clinical characteristics. Arch Ophthalmol. 2003; 121(10):1392-6. DOI: 10.1001/archopht.121.10.1392. View

Bessho H, Honda S, Imai H, Negi A . Natural course and funduscopic findings of polypoidal choroidal vasculopathy in a Japanese population over 1 year of follow-up. Retina. 2011; 31(8):1598-602. DOI: 10.1097/IAE.0b013e31820d3f28. View

Joachim N, Mitchell P, Younan C, Burlutsky G, Cheng C, Cheung C . Ethnic variation in early age-related macular degeneration lesions between white Australians and Singaporean Asians. Invest Ophthalmol Vis Sci. 2014; 55(7):4421-9. DOI: 10.1167/iovs.14-14476. View

Yanagi Y, Foo V, Yoshida A . Asian age-related macular degeneration: from basic science research perspective. Eye (Lond). 2018; 33(1):34-49. PMC: 6328602. DOI: 10.1038/s41433-018-0225-x. View

10.

Cheung C, Lee W, Koizumi H, Dansingani K, Lai T, Freund K . Pachychoroid disease. Eye (Lond). 2018; 33(1):14-33. PMC: 6328576. DOI: 10.1038/s41433-018-0158-4. View

11.

Baek J, Kook L, Lee W . Choriocapillaris Flow Impairments in Association with Pachyvessel in Early Stages of Pachychoroid. Sci Rep. 2019; 9(1):5565. PMC: 6447632. DOI: 10.1038/s41598-019-42052-w. View

12.

Yanagi Y . Pachychoroid disease: a new perspective on exudative maculopathy. Jpn J Ophthalmol. 2020; 64(4):323-337. DOI: 10.1007/s10384-020-00740-5. View

13.

Matsumoto H, Hoshino J, Mukai R, Nakamura K, Kishi S, Akiyama H . Clinical characteristics and pachychoroid incidence in Japanese patients with neovascular age-related macular degeneration. Sci Rep. 2022; 12(1):4492. PMC: 8927155. DOI: 10.1038/s41598-022-08666-3. View

14.

Sasaki M, Kawasaki R, Yanagi Y . Early Stages of Age-Related Macular Degeneration: Racial/Ethnic Differences and Proposal of a New Classification Incorporating Emerging Concept of Choroidal Pathology. J Clin Med. 2022; 11(21). PMC: 9657039. DOI: 10.3390/jcm11216274. View

15.

Terao N, Koizumi H, Kojima K, Yamagishi T, Yamamoto Y, Yoshii K . Distinct Aqueous Humour Cytokine Profiles of Patients with Pachychoroid Neovasculopathy and Neovascular Age-related Macular Degeneration. Sci Rep. 2018; 8(1):10520. PMC: 6043533. DOI: 10.1038/s41598-018-28484-w. View

16.

Edwards A, Ritter 3rd R, Abel K, Manning A, Panhuysen C, Farrer L . Complement factor H polymorphism and age-related macular degeneration. Science. 2005; 308(5720):421-4. DOI: 10.1126/science.1110189. View

17.

Hageman G, Anderson D, Johnson L, Hancox L, Taiber A, Hardisty L . A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci U S A. 2005; 102(20):7227-32. PMC: 1088171. DOI: 10.1073/pnas.0501536102. View

19.

Maugeri A, Barchitta M, Agodi A . The association between complement factor H rs1061170 polymorphism and age-related macular degeneration: a comprehensive meta-analysis stratified by stage of disease and ethnicity. Acta Ophthalmol. 2018; 97(1):e8-e21. DOI: 10.1111/aos.13849. View

20.

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. 2010; 118(2):339-44. DOI: 10.1016/j.ophtha.2010.06.040. View

21.

Arakawa S, Takahashi A, Ashikawa K, Hosono N, Aoi T, Yasuda M . 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. DOI: 10.1038/ng.938. View