Complement factor H Y402H polymorphism and characteristics of exudative age‐related macular degeneration lesions

Abstract

. Purpose: The Y402H polymorphism of the complement factor H (CFH) gene is associated with age‐related macular degeneration (AMD) in many populations. The reported genotype−phenotype correlations in the CFH Y402H polymorphism have not been pronounced and no studies on the effect of the polymorphism on the subgroups within wet AMD have been performed. In this study, we wanted to evaluate whether the CFH Y402H polymorphism has an effect on clinical variables in recent exudative AMD lesions. Methods: The study included 172 patients with exudative AMD. The size of AMD lesions and the presence and area of other AMD lesion variables were recorded in fluorescein angiography (FA) and analysed in relation to the Y402H genotypes. Results: The median lesion size (classic + occult choroidal neovascularization [CNV] + serous pigment epithelium detachment [PED] + haemorrhage, if present) was 8.15 mm2 in patients homozygous for the CFH risk allele (CC), 7.50 mm2 in heterozygous patients (CT), and 7.05 mm2 in those with the normal genotype (TT) (p = 0.599). Areas of classic and occult CNV, combined, without serous PED or haemorrhage were 6.37 mm2, 5.00 mm2 and 5.18 mm2, respectively (p = 0.407). There was a trend for CC patients to have more frequently minimally classic and less frequently predominantly classic lesion composition than CT or TT subjects. Conclusions: We detected no clear impact of the CFH Y402H polymorphism on recent exudative AMD lesion characteristics. Although the complement cascade is implicated in CNV formation and scarring processes in the retina, the Y402H polymorphism appears relatively neutral in these functions.

Pharmacogenetic Influence of LOC387715/HTRA1 on the Efficacy of Bevacizumab Treatment for Age-Related Macular Degeneration in a Korean Population

“…These results are consistent with previous reports in Asian populations [32]. In addition to the association between genotypes and disease pathogenesis [33-35], there have been many reports on CFH polymorphism as a predictor of treatment response in Caucasian populations, such as the response to zinc supplements [36], photodynamic therapy (PDT) [37-39], and intravitreal antivascular endothelial growth factor (VEGF) agents such as intravitreal bevacizumab [40] and ranibizumab treatment [41]. Anti-VEGF, which is now a standard treatment for exudative AMD, causes regression of neovascularization and has an anti-inflammatory effect.…”

Age-related macular degeneration and the complement system

“…Seitsonen et al found no correlation between CNV size and CFH Y402H genotype in patients with wet AMD. However they did find a non-significant association in patients with the homozygous at-risk CC allele and incidence of minimally classic CNV (Seitsonen et al 2008a). Leveziel et al (2008) found individuals with wet AMD, with the homozygous Y402H genotype were more likely to have minimally classic CNV, although numbers were relatively small in each group.…”

Ocular blood flow in diabetes and age-related macular degeneration

“…In Caucasian populations, variants in the complement factor H gene have been shown to be consistently associated with an increased risk for AMD. [66][67][68][69] Although these findings strongly indicate that the innate immune system is implicated in the mechanisms that lead to AMD, other factors have been discussed as well. Among others, a primary vascular component has been proposed as contributing to AMD pathophysiology.…”