Systematic Review and Meta-Analysis of the Association between Complement Factor H I62V Polymorphism and Risk of Polypoidal Choroidal Vasculopathy in Asian Populations
Purpose To investigate whether the polymorphism rs800292 (184G>A, I62V) in the complement factor H gene is associated with polypoidal choroidal vasculopathy (PCV) and the genetic difference between PCV and neovascular age-related macular degeneration (nAMD), in Asian populations. Methods A comprehensive literature search was performed in PubMed, Medline, Web of Science, and reference lists. A system review and meta-analysis of the association between I62V and PCV and/or nAMD were performed from 8 studies involving 5,062 subjects. The following data from individual studies were extracted and analyzed: 1) comparison of I62V polymorphisms between PCV and controls; 2) comparison of I62V polymorphisms between PCV and nAMD. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed-effects models. The Q-statistic test was used to assess heterogeneity, and Egger’s test was used to evaluate publication bias. Sensitivity analysis and cumulative meta-analysis were also performed. Results The I62V polymorphism showed a significant summary OR1 for genotype GA+GG versus homozygous genotype AA was 3.18 (95% CI, 2.51–4.04, P<0.00001), the OR2 of heterozygous genotype GA versus AA was 2.29 (95% CI: 1.79–2.94, P<0.00001), the OR3 of homozygous genotype GG versus AA was 4.42 (95% CI: 3.45–5.67, P<0.00001), and the OR4 of allele G versus A was 2.04 (95% CI: 1.85–2.26, P<0.00001). Sensitivity analysis indicated the robustness of our findings, and evidence of publication bias was not observed in our meta-analysis. Cumulative meta-analysis revealed that the summary ORs were stable. There was no significant difference in every genetic model between PCV and nAMD (n = 5, OR1 = 0.92, OR2 = 0.96, OR3 = 0.90, OR4 = 0.94). Conclusions Our analysis provides evidence that the I62V polymorphism is associated with an increased risk of PCV. The variant of I62V could be a promising genetic biomarker of PCV in Asian populations.
References
[1]
Koh AH; Expert PCV Panel, Chen LJ, Chen SJ, Chen Y, et al. (2013) Polypoidal choroidal vasculopathy: evidence-based guidelines for clinical diagnosis and treatment. Retina 33: 686–716. doi: 10.1097/iae.0b013e3182852446
[2]
Liu Y, Wen F, Huang S, Luo G, Yan H, et al. (2007) Subtype lesions of neovascular age-related macular degeneration in Chinese patients. Graefes Arch Clin Exp Ophthalmol 245: 1441–5. doi: 10.1007/s00417-007-0575-8
[3]
Byeon SH, Lee SC, Oh HS, Kim SS, Koh HJ, et al. (2008) Incidence and clinical patterns of polypoidal choroidal vasculopathy in Korean patients. Jpn J Ophthalmol 52: 57–62. doi: 10.1007/s10384-007-0498-2
[4]
Maruko I, Iida T, Saito M, Nagayama D, Saito K (2007) Clinical characteristics of exudative age-related macular degeneration in Japanese patients. Am J Ophthalmol 144: 15–22. doi: 10.1016/j.ajo.2007.03.047
[5]
Takahashi K, Ishibashi T, Ogur Y, Yuzawa M (2008) [Classification and diagnostic criteria of age-related macular degeneration]. Nippon Ganka Gakkai Zasshi 112: 1076–1084.
[6]
Lim TH, Laude A, Tan CS (2010) Polypoidal choroidal vasculopathy: an angiographic discussion. Eye (Lond) 24: 483–490. doi: 10.1038/eye.2009.323
[7]
Okubo A, Sameshima M, Uemura A, Kanda S, Ohba N (2002) Clinicopathological correlation of polypoidal choroidal vasculopathy revealed by ultrastructural study. Br J Ophthalmol 86: 1093–8. doi: 10.1136/bjo.86.10.1093
[8]
Sho K, Takahashi K, Yamada H, Wada M, Nagai Y, et al. (2003) Polypoidal choroidal vasculopathy: incidence, demographic features, and clinical characteristics. Arch Ophthalmol 121: 1392–1396. doi: 10.1001/archopht.121.10.1392
[9]
Laude A, Cackett PD, Vithana EN, Yeo IY, Wong D, et al. (2010) Polypoidal choroidal vasculopathy and neovascular age-related macular degeneration: same or different disease? Prog Retin Eye Res 29: 19–29. doi: 10.1016/j.preteyeres.2009.10.001
[10]
Lima LH, Schubert C, Ferrara DC, Merriam JE, Imamura Y, et al. (2010) Three major loci involved in age-related macular degeneration are also associated with polypoidal choroidal vasculopathy. Ophthalmology 117: 1567–70. doi: 10.1016/j.ophtha.2009.12.018
[11]
Gotoh N, Yamada R, Nakanishi H, Saito M, Iida T, et al. (2008) 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 Experiment Ophthalmol 36: 437–42. doi: 10.1111/j.1442-9071.2008.01791.x
[12]
Bessho H, Honda S, Kondo N, Negi A (2011) The association of age-related maculopathy susceptibility 2 polymorphisms with phenotype in typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Mol Vis 17: 977–82. doi: 10.1155/2011/742020
[13]
Sakurada Y, Kubota T, Imasawa M, Mabuchi F, Tateno Y, et al. (2011) Role of complement factor H I62V and age-related maculopathy susceptibility 2 A69S variants in the clinical expression of polypoidal choroidal vasculopathy. Ophthalmology 118: 1402–7. doi: 10.1016/j.ophtha.2010.12.010
[14]
Mori K, Horie-Inoue K, Gehlbach PL, Takita H, Kabasawa S, et al. (2010) Phenotype and genotype characteristics of age-related macular degeneration in a Japanese population. Ophthalmology 117: 928–38. doi: 10.1016/j.ophtha.2009.10.001
[15]
Kondo N, Honda S, Kuno S, Negi A (2009) Coding variant I62V in the complement factor H gene is strongly associated with polypoidal choroidal vasculopathy. Ophthalmology 116: 304–10. doi: 10.1016/j.ophtha.2008.11.011
[16]
Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339: b2535. doi: 10.1136/bmj.b2535
[17]
Wigginton JE, Cutler DJ, Abecasis GR (2005) A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet 76: 887–93. doi: 10.1086/429864
[18]
Ioannidis JP, Patsopoulos NA, Evangelou E (2007) Heterogeneity in meta-analyses of genome-wide association investigations. PLoS ONE 2: e841. doi: 10.1371/journal.pone.0000841
Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315: 629–34. doi: 10.1136/bmj.315.7109.629
[21]
Miki A, Honda S, Kondo N, Negi A (2013) The Association of Age-related Maculopathy Susceptibility 2 (ARMS2) and Complement Factor H (CFH) Variants with Two Angiographic Subtypes of Polypoidal Choroidal Vasculopathy. Ophthalmic Genet 34: 146–50. doi: 10.3109/13816810.2012.749288
[22]
Zhang X, Li M, Wen F, Zuo C, Chen H, et al. (2013) 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 108: 16–22. doi: 10.1016/j.exer.2012.12.005
[23]
Ueda-Arakawa N, Ooto S, Nakata I, Yamashiro K, Tsujikawa A, et al. (2013) Prevalence and genomic association of reticular pseudodrusen in age-related macular degeneration. Am J Ophthalmol 155: 260–269.e2. doi: 10.1016/j.ajo.2012.08.011
[24]
Chantaren P, Ruamviboonsuk P, Ponglikitmongkol M, Tiensuwan M, Promso S (2012) Major single nucleotide polymorphisms in polypoidal choroidal vasculopathy: a comparative analysis between Thai and other Asian populations. Clin Ophthalmol. 6: 465–71. doi: 10.2147/opth.s30529
[25]
Tanaka K, Nakayama T, Yuzawa M, Wang Z, Kawamura A, et al. (2011) Analysis of candidate genes for age-related macular degeneration subtypes in the Japanese population. Mol Vis 17: 2751–8.
[26]
Hayashi H, Yamashiro K, Gotoh N, Nakanishi H, Nakata I, et al. (2010) CFH and ARMS2 variations in age-related macular degeneration, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation. Invest Ophthalmol Vis Sci. 51: 5914–9. doi: 10.1167/iovs.10-5554
[27]
Goto A, Akahori M, Okamoto H, Minami M, Terauchi N, et al. (2009) Genetic analysis of typical wet-type age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese population. J Ocul Biol Dis Infor 2: 164–175. doi: 10.1007/s12177-009-9047-1
[28]
Lee KY, Vithana EN, Mathur R, Yong VH, Yeo IY, et al. (2008) Association analysis of CFH, C2, BF, and HTRA1 gene polymorphisms in Chinese patients with polypoidal choroidal vasculopathy. Invest Ophthalmol Vis Sci 49: 2613–9. doi: 10.1167/iovs.07-0860
[29]
Rodríguez de Córdoba S, Esparza-Gordillo J, Goicoechea de Jorge E, Lopez-Trascasa M, Sánchez-Corral P (2004) The human complement factor H: functional roles, genetic variations and disease associations. Mol Immunol 41: 355–67.
[30]
Yuan D, Yang Q, Liu X, Yuan D, Yuan S, et al. (2013) Complement factor H Val62Ile variant and risk of age-related macular degeneration: a meta-analysis. Mol Vis 19: 374–83.
[31]
Chen H, Liu K, Chen LJ, Hou P, Chen W, Pang CP (2012) Genetic associations in polypoidal choroidal vasculopathy: a systematic review and meta-analysis. Mol Vis18: 816–29.
[32]
Liu K, Chen LJ, Tam PO, Shi Y, Lai TY, et al. (2013) Associations of the C2-CFB-RDBP-SKIV2L locus with age-related macular degeneration and polypoidal choroidal vasculopathy. Ophthalmology 120: 837–43. doi: 10.1016/j.ophtha.2012.10.003
[33]
Nakata I, Yamashiro K, Yamada R, Gotoh N, Nakanishi H, et al. (2012) Significance of C2/CFB variants in age-related macular degeneration and polypoidal choroidal vasculopathy in a Japanese population. Invest Ophthalmol Vis Sci53: 794–8. doi: 10.1167/iovs.11-8468
