Purpose
The evidence in the literature of the relationship between the polymorphism of CFH gene represented by changing tyrosine to histidine at position 402 of the CFH gene (Y402H) and the response to treatment of wet AMD using a pro-re-nata (PRN) regimen are controversial. The aim of this study is to compare the functional and morphological evolution of patients with exudative AMD treated with VEGF inhibitors with the Y402H polymorphism of CFH gene in the Brazilian population.
Methods
Forty-six patients who had previously undergone treatment for wet AMD with bevacizumab or ranibizumab in PRN regimen, at four clinical centers in Brazil, in the period from January 2008 to December 2012, were included. Molecular analysis of polymorphisms was performed by polymerase chain reaction (PCR) and direct sequencing. Evolution of visual acuity, central retinal thickness and number of injections over one year of follow-up were correlated to CFH genotypes.
Results
Direct sequencing of the Y402H polymorphism showed that 23.91% of the patients were homozygous for the risk allele (CC), 50% were heterozygous (CT) and 26.08% were homozygous for the wild allele (TT). The analysis of variance for the difference between the logMAR visual acuity at one year, compared to baseline values, showed an improvement in visual acuity at one year (p=0.039). Profile contrast analysis showed this difference was significant only in the group without the C allele (p=0.049), without significance in patients with the risk allele C (p=0.241). Central retinal thickness showed a mean reduction at one year compared to baseline (p<0,001), while significant differences were found in the in CT (p<0,001) and TT (p=0.002) genotypes, whereas in the CC group was not significant (p=0.148). Patients in the CC group underwent an average of 3.4±1.4 injections of VEGF inhibitors over a year of follow-up, while the CT group underwent 3.8±1.9 injections and TT group, 3.8±1.5 injections (p=0.787).
Conclusions
The presence of the risk allele of the Y402H polymorphism in CFH gene is related to less favorable evolution over a year in this Brazilian population with exudative AMD in treatment with VEGF inhibitors in PRN regimen. This pharmacogenetic effect may be influenced by treatment regimen.
Keywords: 412 age-related macular degeneration •
539 genetics •
748 vascular endothelial growth factor