Genetic Variants Affecting Anti-VEGF Drug Response in Polypoidal Choroidal Vasculopathy Patients: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy and Inclusion/Exclusion Criteria
- Manuscripts studying genetic variants affecting anti-VEGF drug response in oncology patients were excluded.
- Manuscripts published in journals not indexed in Journal Citation Reports (JCR) were excluded.
- Manuscripts regarding genetic variants related to the illness and not related to anti-VEGF drug response were excluded.
- Manuscripts studying the association of genetic variants with response to anti-VEGF drugs in non-PCV patients (only) were excluded.
- Manuscripts written in English (only) were included.
- Manuscripts studying the association of genetic variants with patients′ response to anti-VEGF drugs in PCV patients were included.
2.2. Data Extraction and Quality Assessment
2.3. Data Analysis
3. Results
Meta-Analysis
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Ref SNP (rs) | Gene | Drug | Type | Pathology |
---|---|---|---|---|
rs4073 | CXCL8 | bevacizumab | Efficacy | Macular Degeneration |
rs699947 | VEGFA | ranibizumab | Efficacy | Macular Degeneration |
rs3025000 | VEGFA | bevacizumab, ranibizumab | Efficacy | Macular Degeneration |
rs2070296 | NRP1 | ranibizumab | Efficacy | Macular Degeneration |
rs10490924 | ARMS2 | bevacizumab | Efficacy | Macular Degeneration |
rs1061170 | CFH | bevacizumab | Dosage | Macular Degeneration |
rs1061170 | CFH | bevacizumab, ranibizumab | Efficacy | Macular Degeneration |
rs833069 | VEGFA | ranibizumab | Efficacy | Macular Degeneration |
rs11200638 | HTRA1 | bevacizumab, ranibizumab | Efficacy | Macular Degeneration |
rs1061170 | CFH | photodynamic therapy | Efficacy | Macular Degeneration |
rs5985 | F13A1 | photodynamic therapy | Efficacy | Choroidal Neovascularization |
rs2010963 | VGFA | bevacizumab, pegaptanib, ranibizumab | Efficacy | Choroidal Neovascularization |
Author | Ref SNP (rs) | Gene | SNP (Location) | MAF | Genotype mm/Mm/MM | Origin | Treatment | Patients | Follow-Up (Months) |
---|---|---|---|---|---|---|---|---|---|
Park UC et al. [35] | rs800292 | CFH | I62V | 0.290 | 4/46/45 | Korea | Ranibizumab or bevacizumab | PCV | 12 |
rs1061170 | CFH | Y402H | 0.080 | 1/13/81 | Korea | Ranibizumab or bevacizumab | PCV | 12 | |
rs9332739 | C2 | E318D | 0.019 | 1/1/93 | Korea | Ranibizumab or bevacizumab | PCV | 12 | |
rs641153 | CFB | R32Q | 0.081 | 0/14/79 | Korea | Ranibizumab or bevacizumab | PCV | 12 | |
rs429608 | SKIV2L | 3493G/A | 0.088 | 1/13/80 | Korea | Ranibizumab or bevacizumab | PCV | 12 | |
rs699947 | VEGFA | C-2578A | 0.281 | 10/39/45 | Korea | Ranibizumab or bevacizumab | PCV | 12 | |
rs3025039 | VEGFA | C936T | 0.247 | 6/36/53 | Korea | Ranibizumab or bevacizumab | PCV | 12 | |
rs10490924 | ARMS2 | A69S | 0.375 | 12/40/42 | Korea | Ranibizumab or bevacizumab | PCV | 12 | |
rs11200638 | HTRA1 | -625A/G | 0.370 | 12/41/42 | Korea | Ranibizumab or bevacizumab | PCV | 12 | |
rs1136287 | PEDF | Met72Thr | 0.488 | 23/50/22 | Korea | Ranibizumab or bevacizumab | PCV | 12 | |
Park DH et al. [36] | rs10490924 | ARMS2 | A69S | 0.412 | 12/18/21 | Korea | Bevacizumab + PDT | PCV | 12 |
rs11200638 | HTRA1 | -625A/G | 0.382 | 10/19/22 | Korea | Bevacizumab + PDT | PCV | 12 | |
Kawashima Y et al. [37] | rs10490924 | ARMS2 | A69S | 0.316 | 6/12/20 | Japan | 1st Ranibizumab; 2nd Aflibercept | PCV or nAMD | 6 |
rs800292 | CFH | I62V | 0.184 | 2/10/26 | Japan | 1st Ranibizumab; 2nd Aflibercept | PCV or nAMD | 6 | |
rs1061170 | CFH | Y402H | 0.145 | 1/9/28 | Japan | 1st Ranibizumab; 2nd Aflibercept | PCV or nAMD | 6 | |
Hata M et al. [38] | rs10490924 | ARMS2 | A69S | 0.400 | 17/43/45 | Japan | Ranibizumab | PCV or nAMD | 24 |
rs800292 | CFH | I62V | 0.246 | 7/38/61 | Japan | Ranibizumab | PCV or nAMD | 24 | |
Hata M et al. [39] | rs10490924 | ARMS2 | A69S | 0.338 | 10/32/35 | Japan | Ranibizumab + PDT | PCV | 24 |
rs800292 | CFH | I62V | 0.316 | 10/28/38 | Japan | Ranibizumab + PDT | PCV | 24 | |
Nakai S et al. [40] | rs10490924 | ARMS2 | A69S | 0.427 | 9/23/16 | Japan | Aflibercept + PDT | PCV | 12 |
Study | n | Gene | Change | Related Endpoint | p-Value |
---|---|---|---|---|---|
Park UC et al. * [35] | 81 | CFH | I62V | BCVA (Early Treatment Diabetic Retinopathy Study) | 0.039 |
Total Foveal Thickness change | 0.255 | ||||
Pigment Epithelium Detachment (PED) regression on OCT | 0.079 | ||||
81 | CFH | Y402H | BCVA (Early Treatment Diabetic Retinopathy Study) | 0.043 | |
Total Foveal Thickness change | 0.551 | ||||
Pigment Epithelium Detachment (PED) regression on OCT | 0.133 | ||||
80 | ARMS2 | A69S | BCVA (Early Treatment Diabetic Retinopathy Study) | 0.338 | |
Total Foveal Thickness change | 0.212 | ||||
Pigment Epithelium Detachment (PED) regression on OCT | 0.004 | ||||
81 | HTRA1 | -625A/G | BCVA (Early Treatment Diabetic Retinopathy Study) | 0.615 | |
Total Foveal Thickness change | 0.276 | ||||
Pigment Epithelium Detachment (PED) regression on OCT | 0.014 | ||||
Park DH et al. [36] | 51 | ARMS2 | A69S | FA-GLD | 0.004 |
ICGA-GLD | 0.972 | ||||
Complete absence of leakage by FA | 0.04 | ||||
Complete polyp regression by ICGA | 0.006 | ||||
BCVA (Snellen visual acuity) | 0.034 | ||||
51 | HTRA1 | -625A/G | FA-GLD | 0.009 | |
ICGA-GLD | 0.937 | ||||
Complete absence of leakage by FA | 0.019 | ||||
Complete polyp regression by ICGA | 0.002 | ||||
BCVA (Snellen visual acuity) | 0.022 | ||||
Kawashima Y et al. † [37] | 38 | ARMS2 | A69S | Visual acuity change (Landolt chart) | 0.91 |
38 | CFH | I62V | Visual acuity change (Landolt chart) | 0.44 | |
38 | CFH | Y402H | Visual acuity change (Landolt chart) | 0.24 | |
Hata M et al. [38] | 70 | ARMS2 | A69S | BCVA (Landolt chart) | 0.942 |
70 | CFH | I62V | BCVA (Landolt chart) | 0.352 | |
Hata M et al. [39] | 77 | ARMS2 | A69S | BCVA (Landolt chart) at 12 months/24 months | 0.957/0.048 |
76 | CFH | I62V | BCVA (Landolt chart) at 12 months/24 months | 0.439/0.664 | |
Nakai S et al. [40] | 48 | ARMS2 | A69S | BCVA | 0.235 |
Central Retinal Thickness | 0.381 | ||||
Subfoveal Choroidal thickness | 0.133 |
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Díaz-Villamarín, X.; Blánquez-Martínez, D.; Pozo-Agundo, A.; Pérez-Gutiérrez, A.M.; Muñoz-Ávila, J.I.; Antúnez-Rodríguez, A.; Fernández-Gómez, A.E.; García-Navas, P.; Martínez-González, L.J.; Dávila-Fajardo, C.L. Genetic Variants Affecting Anti-VEGF Drug Response in Polypoidal Choroidal Vasculopathy Patients: A Systematic Review and Meta-Analysis. Genes 2020, 11, 1335. https://doi.org/10.3390/genes11111335
Díaz-Villamarín X, Blánquez-Martínez D, Pozo-Agundo A, Pérez-Gutiérrez AM, Muñoz-Ávila JI, Antúnez-Rodríguez A, Fernández-Gómez AE, García-Navas P, Martínez-González LJ, Dávila-Fajardo CL. Genetic Variants Affecting Anti-VEGF Drug Response in Polypoidal Choroidal Vasculopathy Patients: A Systematic Review and Meta-Analysis. Genes. 2020; 11(11):1335. https://doi.org/10.3390/genes11111335
Chicago/Turabian StyleDíaz-Villamarín, Xando, David Blánquez-Martínez, Ana Pozo-Agundo, Ana María Pérez-Gutiérrez, José Ignacio Muñoz-Ávila, Alba Antúnez-Rodríguez, Ana Estefanía Fernández-Gómez, Paloma García-Navas, Luis Javier Martínez-González, and Cristina Lucía Dávila-Fajardo. 2020. "Genetic Variants Affecting Anti-VEGF Drug Response in Polypoidal Choroidal Vasculopathy Patients: A Systematic Review and Meta-Analysis" Genes 11, no. 11: 1335. https://doi.org/10.3390/genes11111335