rs1061170

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.

Prospective cohort study of 472 elderly French participants (mean age 81.9 years) from the ALIENOR study examining incident reticular pseudodrusen (RPD). Annual incidence was 2.047% with estimated 5-year cumulative incidence of 9.73%. Risk factors identified in multivariate analysis included ARMS2 rs10490924 (HR 3.36, p=0.0009), LIPC rs10468017 (HR 2.65, p=0.0029), and thinner choroidal thickness (HR 1.06, p=0.0085). Liposoluble statin medication was protective (HR 0.18, p=0.0448).

This prospective cohort study (Münster Aging and Retina Study, MARS) analyzed genetic variants in CFH (rs1061170), ARMS2 (rs10490924), and ABCA1 (rs1883025) in relation to drusen phenotypes and progression in early age-related macular degeneration. Cross-sectionally, CFH and ARMS2 risk variants were associated with drusen features, while longitudinally over 2.6 years, ABCA1 showed inverse association with drusen progression (OR=0.54) and CFH showed positive association with intermediate-to-high drusen progression (OR=2.33).

A prospective nested case-control study pooled from five large cohorts examining 15 CX3CR1 SNPs (including T280M and V249I) in 1,110 AMD cases (369 neovascular AMD) and 2,532 controls. No significant associations with AMD were found for the candidate variants T280M (RR=0.87, P=0.074) or V249I (RR=1.01, P=0.82) after multiple comparisons correction. Some CX3CR1 variants showed nominal associations with neovascular AMD in recessive models (rs2669845 RR=3.10 P=0.035, rs9868689 RR=0.31 P=0.017, rs2853707 RR=0.48 P=0.050), with possible gene-environment and gene-gene interactions identified.

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 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.

This case-control association study examined CFH Y402H (rs1061170) and ARMS2 A69S (rs10490924) variants in 67 patients with reticular macular disease (RMD), a subphenotype of age-related macular degeneration (AMD), versus 64 matched AMD patients without RMD. The CFH 402H allele frequency was significantly lower in RMD patients (39.6% vs 58.6%; OR=0.46, P=0.003), suggesting protection against RMD despite being an AMD risk allele. Conversely, ARMS2 69S showed enrichment in RMD (44.0% vs 31.3%; OR=1.73, P=0.045), indicating increased RMD risk.

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.

PhD thesis describing comprehensive genome-wide association studies of acute anterior uveitis (AAU) in European (2,752 cases, 3,836 controls) and East Asian (821 cases, 4,898 controls) populations. European descent GWAS identified HLA-B at genome-wide significance plus 11 suggestive loci (ERAP1, NOS2, MERTK). East Asian GWAS identified HLA-B and ERAP1 at genome-wide significance plus 12 suggestive loci (GPR68, RHBDD2). Mendelian randomization confirmed ERAP1 as functionally relevant and showed genetically predicted CRP levels positively associated with AAU risk.

A case-control study investigating whether AMD-associated genetic variants predict treatment response. In 170 dry AMD patients treated with antioxidant supplements, CFH Y402H (rs1061170) carriers had significantly lower response rates (51.7% heterozygous/homozygous vs 75% wild-type, p=0.005), while protective variants in C2 (rs9332739) and CFB (rs4151667, rs2072633) showed improved response. In 52 neovascular AMD patients treated with ranibizumab, ARMS2 A69S (rs10490924) carriers had worse outcomes (46.4% responders vs 87.5% wild-type, p=0.002).

A pathway-focused genetic analysis identified associations between complement pathway genes and age-related macular degeneration (AMD) subtypes using 146 AMD cases and controls. The study confirmed the previously identified CFH Y402H variant (rs1061170) strongly associated with AMD (OR 0.16-0.35 for protection), and identified two additional complement pathway genes—C7 and MBL2—potentially associated with disease progression, particularly the C7 H2 haplotype (rs2329434/rs2876849 variants) that conferred protection against wet AMD among CFH 402H homozygotes (p=0.001, OR 0.16, 95% CI 0.05-0.49).

This methods paper describes the development and validation of sequence-specific primer PCR and restriction fragment length polymorphism (RFLP) assays for genotyping three functional polymorphisms in the complement factor H (CFH) gene: rs800292 (V62I), rs1061170 (Y402H), and rs1065489 (E936D). The assays were validated in 271 healthy Hungarian blood donors, with allele frequencies (257G=0.850, 1277T=0.574, 2881G=0.839) consistent with prior reports. The authors identified strong linkage disequilibrium between the Y402H and E936D variants, and found the high-risk haplotype (257G-1277C-2881G) in 16.2% of their young healthy population.

This is a comprehensive review of the complement factor H (FH) protein family and its role in preventing self-damage from dysregulation of the complement alternative pathway. The paper examines genetic variants in CFH and factor H-related genes (CFHR1-CFHR5) that predispose to age-related macular degeneration, atypical hemolytic uremic syndrome, C3 glomerulopathies, and IgA nephropathy. Key findings include the role of FHR proteins as complement antagonists that compete with FH, and how genetic variations including deletions (ΔCFHR3-CFHR1), hybrid genes, and altered protein expression contribute to disease pathogenesis.

This study documents ethnic variation in the CFH p.Tyr402His (rs1061170, c.1204T>C) polymorphism, a known AMD risk factor (OR ~2.5-4.6 in Caucasians). The risk allele C frequency varies widely across populations: Japanese 7%, Hispanic 17%, African American 35%, Caucasian 34%, and Somali 34%. The findings suggest additional genetic or protective factors beyond CFH contribute to the ethnic differences in AMD prevalence.

A case-control study of 146 Japanese exudative age-related macular degeneration (ARMD) patients and 105 controls examined complement factor H (CFH) gene polymorphisms. The study identified 61 polymorphisms in the CFH gene but found no association between rs1061170 (Y402H, χ² = 3.19, P = 0.423) or other CFH variants and exudative ARMD in Japanese, despite this SNP showing strong association in Caucasians (χ² = 110.96, P < 10⁻²⁴). The absence of CFH association in Japanese may reflect ethnic differences in ARMD phenotypes and genetic architecture.