Predictive role of coagulation-balance gene polymorphisms in the efficacy of photodynamic therapy with verteporfin for classic choroidal neovascularization secondary to age-related macular degeneration

Abstract

These results provide evidences for the presence of pharmacogenetic relationship between peculiar coagulation-balance gene polymorphisms and different levels of PDT-V effectiveness in patients with AMD-related CNV.

Coagulation Gene Predictors of Photodynamic Therapy for Occult Choroidal Neovascularization in Age-Related Macular Degeneration

“…Recently, in Caucasian patients with classic or predominantly classic CNV secondary to AMD, Parmeggiani et al 39 documented the presence of significant predictive associations among diverse levels of PDT-V effectiveness and peculiar coagulation-balance SNPs: (1) the carriers of thrombophilic gene variants, directly predisposing to thrombosis through a higher thrombin generation (i.e., FVL-G1691A and FII-G20210A) or indirectly affecting thrombocoagulative functionality via hyperhomocysteinemic activation of endothelial cells and platelets (i.e., MTHFR-C677T), were characterized by a greater possibility of showing a benefit after PDT-V; (2) the PDT-V nonresponders were clearly overrepresented within the carriers of the FXIIIA 185 T-allele, which induces an antithrombophilic diathesis that reduces the fibrin-clot stability. 39 In the present study cluster, treated with PDT-V for occult CNV with no classic component, the same methodological approach was used to investigate these pharmacogenetic predictors, but the results just partially confirm those in the prior study. In fact, considering both classic and occult CNVs, FV-1691AϩFII-20210A and, most of all, FXIIIA-185T covariates seem to be predictive of, respectively, clinical success or failure of PDT-V; whereas higher odds of photodynamic benefit is recordable in classic-CNV patients with MTHFR-C677T mutation, but not in occult-CNV patients with the same SNP.…”

“…29 -38 Although the well-known, therapeutic effect of PDT-V is based on a photochemical perturbation of the hemostasis and coagulation within the neovascular complex, only recently we have documented the presence of predictive correlations between peculiar coagulation-balance gene polymorphisms and different levels of PDT-V responsiveness in patients with AMD who have classic or predominantly classic CNV. 39 The purpose of this study was to investigate the predictive role of single nucleotide polymorphisms (SNPs) that encode enzymes involved in coagulation, fibrinolysis, and/or thrombosis in the extent of the benefit that will be realized by the application of standardized PDT-V in Caucasian patients with AMD, complicated by subfoveal occult CNV with no classic component. For this reason, we have examined the short-term variability of angiographic findings after the first PDT-V, considering its putative association with several common or uncommon gene variants, schematically shared in two typologies: (1) gain-of-function SNPs directly influencing the coagulation…”

Platelets, photosensitizers, and PDT

“…Of six gene polymorphisms genotyped, thrombophilic factor V G1691A, factor XIII-A G185T, methionine synthase A2756G, methionine synthase reductase A66G, methylenetetrahydrofolate reductase C677T and prothrombin G20210A, the latter two were identified to be more prevalent within responders. Hyperfibrinolytic factor XIII-A G185T was clearly overrepresented in the nonresponder fraction [176,177].…”

Genetics in Age-Related Macular Degeneration

“…Variants in genes predisposing to hypercoagulability, including prothrombin 20210A and factor V 1691A alleles, have been associated with improved responses to therapy, and the C677T polymorphism in the gene for methylenetetrahydrofolate reductase associates with increased responses in classic CNV. 95,96 Rather unsurprisingly, variations predisposing to increased fibrinolysis, notably the G185T mutation of factor XIII-A, have been linked to nonresponse to treatment. 95,96 Dry Age-Related Macular Degeneration…”

“…95,96 Rather unsurprisingly, variations predisposing to increased fibrinolysis, notably the G185T mutation of factor XIII-A, have been linked to nonresponse to treatment. 95,96 Dry Age-Related Macular Degeneration…”