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

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 50 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) 3.62, P-c < 0.0001) was similar to that reported in other Caucasian cohorts. The magnitude and strength of this association was stronger in AREDS stages 2-4 (ORs = 4.48, 2.69, and 5.17). ORs for the risk of predominantly classic CNV were significantly raised for both the CC (OR 17.87, P < 0.0001) and CT (OR = 9.06, P = 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 = 2.16, P = 0.011), and presence of the CC genotype significantly increased the risk of PDT (OR = 5.48, P = 0.015). The degree of visual loss following PDT was significantly higher in the CFH CC genotype group (P = 0.038); 50% of CC cases (n = 13) and 45% of the CTcases (n = 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