rs11200638

Cross-sectional study of 835 CATT participants with neovascular AMD genotyped for SNPs in CFH, ARMS2, C3, LIPC, CFB, and C2. ARMS2 risk alleles were associated with larger total lesions (p=0.03) and increased intraretinal fluid (p=0.008); C3 risk alleles were associated with decreased intraretinal fluid (p=0.001) and retinal thickness (p=0.02); CFH risk alleles were associated with decreased total thickness (p=0.01).

This study evaluated 835 neovascular age-related macular degeneration (nAMD) patients from the CATT trial for associations between 8 SNPs in the VEGF signaling pathway (7 in VEGF-A: rs699946, rs699947, rs833069, rs833070, rs1413711, rs2010963, rs2146323; 1 in VEGFR-2: rs2071559) and response to anti-VEGF therapy with ranibizumab or bevacizumab. While four VEGF-A SNPs showed nominal associations with retinal thickness (p=0.03-0.04 and p=0.006), adjusted p-values were not statistically significant (p=0.24-0.45). The study found no pharmacogenetic associations between these VEGF pathway SNPs and visual acuity, anatomical outcomes, or injection frequency, concluding that these variants do not substantially influence response to anti-VEGF therapy.

This case-control study of 1844 unrelated white individuals examined the association between 8 SNPs in 5 genes (CFH, HTRA1/LOC387715, C2, CFB, C3) and advanced age-related macular degeneration (AMD), including geographic atrophy and choroidal neovascularization. All genetic variants showed strong associations with AMD, with odds ratios ranging from 0.44 (C2 rs9332739, protective) to 10.99 (HTRA1/LOC387715 rs10490924 TT). A combined predictive model including genetic variants and environmental factors (smoking, age, BMI) achieved 78.8% discrimination accuracy with ROC curve AUC of 0.82.

Comprehensive review evaluating SNPs as genetic predictors of choroidal neovascularization (CNV) response to photodynamic therapy with verteporfin (PDT-V). The paper examines pharmacogenetic correlations for thrombo-coagulative pathway variants (MTHFR rs1801133, F5 rs6025, F2 rs1799963, F13A1 rs5985), complement/inflammatory variants (CFH, HTRA1, CRP, ARMS2), and VEGFA variants (rs699947, rs2146323), concluding that specific SNPs show clinical plausibility as markers to optimize PDT-V efficacy and guide therapeutic approaches in neovascular macular degeneration.

This study characterizes the complex indel in ARMS2 3'UTR associated with age-related macular degeneration (AMD), showing it consists of two side-by-side indels separated by 17 bp and strongly associated with AMD risk (OR=2.13, p=1.89×10⁻¹³). However, quantitative PCR analysis reveals no significant correlation between the indel genotype and ARMS2 mRNA levels in retina or blood samples, suggesting the non-synonymous variant rs10490924 (A69S) is the likely functional risk allele.

This case-control study evaluated 10 AMD-associated SNPs in 4 genes (CFI, COL8A1, LIPC, APOE) and their association with choroidal neovascularization in highly myopic Spanish Caucasian patients (147 mCNV, 103 HM without CNV, 181 controls). SNPs rs13095226 and rs669676 in COL8A1 showed significant associations in univariate analysis (OR=2.0 and 2.4 respectively), but lost significance after Bonferroni correction. Meta-analysis of rs669676 confirmed association with myopic CNV. Only age and hypertension remained significant in multivariate analysis.

This cumulative PhD dissertation investigates genetic susceptibility factors for age-related macular degeneration (AMD). The study confirms weak associations of APOE coding variants with AMD risk (P < 0.05) but finds no association with HMCN1 variants. Large replication studies of candidate genes TLR3 and SERPING1 (1,080-4,881 cases and 2,669-2,842 controls) show no association. The authors identified 15 high-risk variants in ARMS2/HTRA1 region on chromosome 10q23.33-10qter, with the ARMS2 A69S variant showing 2.7-fold increased risk heterozygously and 8.2-fold increased risk homozygously, comparable in strength to CFH Y402H. An indel variant (c.*372_815del443ins54) in ARMS2 3' UTR causes mRNA destabilization.