Korean J Ophthalmol.  2012 Dec;26(6):414-422. 10.3341/kjo.2012.26.6.414.

Pharmacogenetic Influence of LOC387715/HTRA1 on the Efficacy of Bevacizumab Treatment for Age-Related Macular Degeneration in a Korean Population

• Kang HK
• Yoon MH
• Lee DH
• Chin HS

• KMID: 1499678
• DOI: http://doi.org/10.3341/kjo.2012.26.6.414

Abstract

PURPOSE
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.

Keyword

Bevacizumab; Complement factor H Y402H; HTRA1; LOC387715; Macular degeneration

MeSH Terms

Aged
Alleles
Angiogenesis Inhibitors/administration & dosage/therapeutic use
Antibodies, Monoclonal, Humanized/*administration & dosage/therapeutic use
DNA/*genetics
Female
Follow-Up Studies
Genotype
Humans
Intravitreal Injections
Macular Degeneration/drug therapy/epidemiology/*genetics
Male
Pharmacogenetics/*methods
*Polymorphism, Genetic
Retrospective Studies
Serine Endopeptidases/*genetics/metabolism
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Visual Acuity
Angiogenesis Inhibitors
Antibodies, Monoclonal, Humanized
Vascular Endothelial Growth Factor A
DNA
Serine Endopeptidases

Figure

• 

  Fig. 1 Mean logarithm of minimum angular resolution (logMAR) visual improvement in patients with the LOC387715 genotype treated with bevacizumab (black line, TT genotype; grey line, GT genotype; broken line, GG genotype) over a 12 month follow-up period. Visual improvement was greatest in the LOC387715 TT genotype group compared to other groups, at both six months (p = 0.037) and 12 months (p = 0.058) post-treatment.

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