title: 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: OBJECTIVE
  Age-related macular degeneration (AMD) represents the leading cause of blindness in Western populations. The majority of severe vision loss occurs in the exudative form of AMD, characterized by the development of choroidal neovascularization (CNV) beneath the fovea. Photodynamic therapy with verteporfin (PDT-V) represents one of the most largely employed modality that maybe achieves the subfoveal CNV inactivation in AMD patients. Although several ocular factors have been hitherto investigated as predictors, these researches have weakly contributed to PDT-V optimization. As PDT-V benefit is determined by CNV photothrombosis, we have retrospectively studied several coagulation-balance gene polymorphisms as predictors of PDT-V efficacy.
  
  
  METHODS
  Ninety Caucasian patients with neovascular AMD were subdivided in responder and nonresponder, on the basis of CNV responsiveness to PDT-V application. Six gene polymorphisms, that is factor V G1691A, prothrombin G20210A, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and methionine synthase reductase A66G, were genotyped in the entire cohort.
  
  
  RESULTS
  Logistic regression models showed that PDT-V responders were more prevalent within patients with prothrombin G20210A mutation [odds ratio (OR)=5.6, 95% confidence interval (CI) (1.2, 27.2), P=0.03], and within methylenetetrahydrofolate reductase 677T carriers [OR=6.9, 95% CI (2.7, 18.1), P<0.001]. Conversely, PDT-V nonresponders were overrepresented in carriers for factor XIII-A 185T [OR=0.13, 95% CI (0.05, 0.36), P<0.001].
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology, Center Study for Hemostasis and Thrombosis, University of Ferrara, Ferrara, Italy. francesco.parmeggiani@unife.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Parmeggiani
authors.forename: Ciro
authors.initials: C
authors.lastname: Costagliola
authors.forename: Donato
authors.initials: D
authors.lastname: Gemmati
authors.forename: Sergio
authors.initials: S
authors.lastname: D'Angelo
authors.forename: Paolo
authors.initials: P
authors.lastname: Perri
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Scapoli
authors.forename: Linda
authors.initials: L
authors.lastname: Catozzi
authors.forename: Federica
authors.initials: F
authors.lastname: Federici
authors.forename: Adolfo
authors.initials: A
authors.lastname: Sebastiani
authors.forename: Carlo
authors.initials: C
authors.lastname: Incorvaia
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D001779:Blood Coagulation Factors / Q000235:genetics*; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D005165:Factor V / Q000235:genetics; D005176:Factor XIII / Q000235:genetics; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008268:Macular Degeneration / Q000150:complications / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D010597:Pharmacogenetics; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011166:Porphyrins / Q000627:therapeutic use*; D011516:Prothrombin / Q000235:genetics; D012189:Retrospective Studies; D000077362:Verteporfin
chemical_list: D001779:Blood Coagulation Factors; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D005165:Factor V; D011516:Prothrombin; D005176:Factor XIII; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase