title: Pharmacogenetic influence of LOC387715/HTRA1 on the efficacy of bevacizumab treatment for age-related macular degeneration in a Korean population.
abstract: OBJECTIVE
  The purpose of this study was to determine the pharmacogenetic effects of complement factor H (CFH) Y402H, LOC387715 and high-temperature requirement factor A1 (HTRA1) genotypes on the treatment of exudative age-related macular degeneration (AMD) by intravitreal bevacizumab injection in a Korean population.
  
  
  METHODS
  Seventy-five patients diagnosed with exudative AMD were treated with intravitreal bevacizumab (2.5 mg) monotherapy. All patients received three initial intravitreal bevacizumab injections every four weeks and were then treated "as needed" based on clinical findings, optical coherence tomography and fluorescein angiography during the 12 month follow-up period after the third injection.
  
  
  RESULTS
  The difference in visual acuity improvement among the three genotypes of LOC387715 were statistically significant at six months post-treatment (logarithm of the minimum angle of resolution; TT, 0.346; GT, 0.264; GG, 0.188; p = 0.037). Among the LOC387715 genotypes, the number of additional injections was lower in patients who had the risk T allele (GG, 2.143; GT, 2.000; TT, 1.575; p = 0.064). There was no significant difference between visual acuity and central macular thickness change in the CFH Y402H polymorphism group during the 12 month follow-up period. However, the TC group of CFH Y402H required more additional bevacizumab injections than the TT group (TT, 1.517; TC, 3.363; p = 0.020).
  
  
  CONCLUSIONS
  This study demonstrated that different LOC387715/HTRA1 genotypes resulted in different bevacizumab treatment responses on exudative AMD. Patients with the risk allele had an improved treatment response and less need for additional injections. However, patients with the CFH Y402H risk allele needed more additional injections of bevacizumab in order to improve visual acuity. This study illustrates how pharmacogenetic factors may help determine treatment modality and dosing. This could ultimately provide basic data for 'personalized medicine' in AMD.
authors.affiliation: Department of Ophthalmology and Inha Vision Science Laboratory, Inha University School of Medicine, Incheon, Korea.
authors.forename: Haeng Ku
authors.initials: HK
authors.lastname: Kang
authors.forename: Myung Hun
authors.initials: MH
authors.lastname: Yoon
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Lee
authors.forename: Hee Seung
authors.initials: HS
authors.lastname: Chin
mesh_terms: D000368:Aged; D000483:Alleles; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000627:therapeutic use; D000068258:Bevacizumab; D004247:DNA / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D004247:DNA; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases