An analysis of the CFH Y402H genotype in AMD patients and controls from the UK, and response to PDT treatment

Abstract

Aim Mutation in the complement factor H (CFH) gene is an important risk factor for age-related macular degeneration (AMD). In this study, we identified the strength of the CFH Y402H gene variant association in a UK AMD cohort and tested the hypothesis that this variant may influence the biological response of choroidal neovascularisation (CNV) following photodynamic therapy (PDT) for CNV. Methods A total of 557 cases with AMD and 551 normal controls were genotyped for the CFH Y402H (1277 C/T) variant using the 5 0 nuclease TaqMan assay for allelic discrimination. The CFH gene association for AMD, for the different CNV subtypes and for patients needing PDT was estimated. Twenty-seven PDT-treated patients were followed up for 15 months with ETDRS-derived vision, clinical examination, and fundus angiography. Individuals with different CFH genotypes were then analysed for any association with visual change following PDT. Results The risk association for AMD with the CFH CC genotype (odd ratio (OR) ¼ 3.62, P c o0.0001) was similar to that reported in other Caucasian cohorts. The magnitude and strength of this association was stronger in AREDS stages 2-4 (ORs ¼ 4.48, 2.69, and 5.17). ORs for the risk of predominantly classic CNV were significantly raised for both the CC (OR ¼ 17.87, Po0.0001) and CT (OR ¼ 9.06, P ¼ 0.0002) genotypes. The number of patients carrying the high-risk C allele was 70.4% in those requiring PDT as compared to 52.3% in the non-PDT group (OR ¼ 2.16, P ¼ 0.011), and presence of the CC genotype significantly increased the risk of PDT (OR ¼ 5.48, P ¼ 0.015). The degree of visual loss following PDT was significantly higher in the CFH CC genotype group (P ¼ 0.038); 50% of CC cases (n ¼ 13) and 45% of the CT cases (n ¼ 12) lost 15 or more ETDRS letters at final follow-up. Conclusion In this UK cohort of AMD patients, the CFH Y402H variant was significantly enriched in patients with predominantly classic CNV. Patients homozygous for the CFH Y402H genotype seem to have worse visual acuity after PDT.

Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to photodynamic therapy

“…We found a significant difference in the percentage of eyes in each CFH genotype group with predominantly classic lesions, consistent with our and other earlier reports, [10][11][12] which found a higher percentage of predominantly classic lesions in the CFH CFH, complement factor H; PDT, photodynamic therapy; SD, standard deviation; VA, visual acuity. The P-value is from a one-way analysis of variance that compares means of the variables between genotypes using a Bonferroni multiple comparison correction.…”

“…While a small number of reports have correlated AMD clinical phenotypes with CFH Y402H genotype, 10-12 with one study demonstrating a possible association between PDT response and CFH genotype, 11 there are still few data available regarding such genotype-phenotype correlations.…”

“…[2][3][4][5] The presence of the CFH Y402H polymorphism correlates with both exudative 6,7 and advanced atrophic 8 AMD, as well as AMD progression, 9 but limited data are available evaluating AMD phenotypes or response to treatment with regard to CFH genotype. [10][11][12][13] The association of AMD with two distinct polymorphisms within chromosome 10q26 has identified this region as a second major locus contributing to AMD pathogenesis. The non-synonymous SNP rs10490924, predicted to result in a coding variation (A69S) within the hypothetical gene LOC387715, was found to confer an increased risk for development of AMD, 14,15 and this locus has been renamed ARMS2 (age-related maculopathy susceptibility gene 2).…”

“…[10][11][12] The purpose of this study was to evaluate the potential association between response to treatment for neovascular AMD with PDT and the CFH Y402H variant. We also examined one of the chromosome 10q polymorphic loci, LOC387715 A69S, for any relationship to treatment response.…”

Positive Association of Complement Factor H Gene Variants with the Effect of Photodynamic Therapy in Polypoidal Choroidal Vasculopathy

“…Recently, genetic variants in the complement factor H (CFH) gene on chromosome 1q32 have been tested to explain the response to PDT [10][11][12][13][14]. In particular, the Y402H coding variant (rs1061170) in CFH is presumed to have functional consequences consistent with AMD pathology [15][16][17][18][19] and most studies have been conducted to find that CFH Y402H correlates with the outcome of PDT [10][11][12][13][14]. In neovascular AMD, Brantley et al [12] reported an association of the CFH Y402H variant with the visual outcome after PDT [12].…”