Pharmacogenetic Aspects in Therapeutic Management of Subfoveal Choroidal Neovascularisation: Role of Factor XIII-A 185 T-Allele

Author(s): Francesco Parmeggiani, Ciro Costagliola, Carlo Incorvaia, Adolfo Sebastiani, Donato Gemmati

Journal Name: Current Drug Targets

Volume 12 , Issue 2 , 2011


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Abstract:

In Western Countries, the occurrence of choroidal neovascularization (CNV) secondary to different forms of macular degeneration represents a common cause of blindness. Particularly, age-related macular degeneration (AMD) and pathologic myopia (PM) are the most frequent diseases related to CNV development. At present, the combined employment of drugs acting against vascular endothelial growth factor (anti-VEGF) and photodynamic therapy with verteporfin (PDT-V) is a promising therapeutic strategy for neovascular macular degenerations. However, this approach inevitably leads to an increase in health-resource utilization. In several clusters of patients treated for CNV, correlations among common gene polymorphisms implicated in coagulation- or complement-cascade and different levels of, respectively, post-PDT-V or post-anti-VEGF benefit have been reported. Factor XIII-A G185T substitution (rs5985), a frequent anti-thrombophilic genetic variant of Caucasian ethnic groups, unequivocally influences a worsening of the CNV responsiveness to PDT-V in patients affected by either AMD- or PM-related CNV. These coherent pharmacogenetic findings point out the opportunities to: i. optimize the eligibility criteria of PDT-V and, ii. customize the interventional strategy against CNV, for finally minimizing the socio-economic burden of neovascular macular degenerations.

Keywords: Macular degenerations, choroidal neovascularization, pharmacogenetics, photodynamic therapy with verteporfin, fibrin-clot stability, factor XIII-A G185T gene polymorphism, anti-thrombophilia, pathologic myopia (PM), vascular endothelial growth factor, genetic variant, Caucasian ethnic groups, degenerative retinal diseases, age-related, fluorescein angiography, retinal pigment epithelium, pegaptanib, ranibizumab, bevacizumab, thermal laser-photocoagu-lation, submacular surgery, methylenetetrahydrofolate reductase C677T (MTHFR-C677T; rs1801133), methionine synthase, methionine synthase reductase A66G (MTRR-A66G; rs1801394), reductase A66G (MTRR-A66G; rs1801394), hyper-homocysteinemic MTHFR 677 T-allele, thromboxane A2, histamine, prostaglandins, tumor necrosis factor, transglutaminase factor XIII (FXIII), Hyperhomocysteinemia, Hypoxia

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Article Details

VOLUME: 12
ISSUE: 2
Year: 2011
Published on: 01 March, 2012
Page: [138 - 148]
Pages: 11
DOI: 10.2174/138945011794182773
Price: $65

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