Pharmacogenetic Influence of LOC387715/HTRA1 on the Efficacy of Bevacizumab Treatment for Age-Related Macular Degeneration in a Korean Population
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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.
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.
참고문헌 (50)
- De Jong PT, "Age-related macular degeneration", N Engl J Med, 355, pp.1474~1485 (2006)
- Ambati J, "Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies", Surv Ophthalmol, 48, pp.257~293 (2003)
- Ferris FL 3rd, "Age-related macular degeneration and blindness due to neovascular maculopathy", Arch Ophthalmol, 102, pp.1640~1642 (1984)
- Friedman DS, "Prevalence of age-related macular degeneration in the United States", Arch Ophthalmol, 122, pp.564~572 (2004)
- Age-Related Eye Disease Study Research Group, "Risk factors associated with age-related macular degeneration. A case-control study in the age-related eye disease study: Age-Related Eye Disease Study report number 3", Ophthalmology, 107, pp.2224~2232 (2000)
- Cackett P, "Smoking, cardiovascular risk factors, and age-related macular degeneration in Asians: the Singapore Malay Eye Study", Am J Ophthalmol, 146, pp.960~967 (2008)
- Dandekar SS, "Does smoking influence the type of age related macular degeneration causing visual impairment?", Br J Ophthalmol, 90, pp.724~727 (2006)
- Peeters A, "Changes in abdominal obesity and age-related macular degeneration: the Atherosclerosis Risk in Communities Study", Arch Ophthalmol, 126, pp.1554~1560 (2008)
- Seddon JM, "Cigarette smoking, fish consumption, omega-3 fatty acid intake, and associations with age-related macular degeneration: the US Twin Study of Age-Related Macular Degeneration", Arch Ophthalmol, 124, pp.995~1001 (2006)
- Smith W, "Risk factors for age-related macular degeneration: pooled findings from three continents", Ophthalmology, 108, pp.697~704 (2001)
- Klein R, "The epidemiology of age-related macular degeneration", Am J Ophthalmol, 137, pp.486~495 (2004)
- Seddon JM, "Familial aggregation of age-related maculopathy", Am J Ophthalmol, 123, pp.199~206 (1997)
- Gorin MB, "A clinician’s view of the molecular genetics of age-related maculopathy", Arch Ophthalmol, 125, pp.21~29 (2007)
- Mullins RF, "Genetic insights into the pathobiology of age-related macular degeneration", Int Ophthalmol Clin, 47, pp.1~14 (2007)
- Swaroop A, "Genetic susceptibility to age-related macular degeneration: a paradigm for dissecting complex disease traits", Hum Mol Genet, 16(2), pp.174~182 (2007)
- Seddon JM, "The US twin study of age-related macular degeneration: relative roles of genetic and environmental influences", Arch Ophthalmol, 123, pp.321~327 (2005)
- Hammond CJ, "Genetic influence on early age-related maculopathy: a twin study", Ophthalmology, 109, pp.730~736 (2002)
- Edwards AO, "Complement factor H polymorphism and age-related macular degeneration", Science, 308, pp.421~424 (2005)
- Haines JL, "Complement factor H variant increases the risk of age-related macular degeneration", Science, 308, pp.419~421 (2005)
- Klein RJ, "Complement factor H polymorphism in age-related macular degeneration", Science, 308, pp.385~389 (2005)
- Conley YP, "CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses", Hum Mol Genet, 15, pp.3206~3218 (2006)
- Hageman GS, "A common haplotype in the complement regulatory gene factor H (HF1", CFH) predisposes individuals to age-related macular degeneration, 2005, pp.102, 7227~7232
- Maller J, "Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration", Nat Genet, 38, pp.1055~1059 (2006)
- Postel EA, "Complement factor H increases risk for atrophic age-related macular degeneration", Ophthalmology, 113, pp.1504~1507 (2006)
- Tuo J, "Synergic effect of polymorphisms in ERCC6 5’ flanking region and complement factor H on age-related macular degeneration predisposition", Proc Natl Acad Sci U S A, 103, pp.9256~9261 (2006)
- Dewan A, "HTRA1 promoter polymorphism in wet age-related macular degeneration", Science, 314, pp.989~992 (2006)
- Yang Z, "A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration", Science, 314, pp.992~993 (2006)
- Yoshida T, "HTRA1 promoter polymorphism predisposes Japanese to age-related macular degeneration", Mol Vis, 13, pp.545~548 (2007)
- Klein R, "Racial", ethnic differences in age-related maculopathy. Third National Health and Nutrition Examination Survey, 1995, pp.102, 371~381
- Gotoh N, "No association between complement factor H gene polymorphism and exudative age-related macular degeneration in Japanese", Hum Genet, 120, pp.139~143 (2006)
- Kim NR, "Association between complement factor H gene polymorphisms and neovascular age-related macular degeneration in Koreans", Invest Ophthalmol Vis Sci, 49, pp.2071~2076 (2008)
- Lee SJ, "LOC387715", HTRA1 polymorphisms, smoking and combined effects on exudative age-related macular degeneration in a Korean population, 2010, pp.38, 698~704
- Andreoli MT, "Comprehensive analysis of complement factor H and LOC387715", ARMS2, Am J Ophthalmol, pp.2009, 148[DOI]
- Leveziel N, "Genotypic influences on severity of exudative age-related macular degeneration", Invest Ophthalmol Vis Sci, 51, pp.2620~2625 (2010)
- Seitsonen S, "Complement factor H Y402H polymorphism and characteristics of exudative age-related macular degeneration lesions", Acta Ophthalmol, 86, pp.390~394 (2008)
- Klein ML, "CFH andLOC387715", ARMS2 genotypes and treatment with antioxidants and zinc for age-related macular degeneration, 2008, pp.115, 1019~1025
- Brantley MA Jr, "Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to photodynamic therapy", Eye (Lond), 23, pp.626~631 (2009)
- Goverdhan SV, "An analysis of the CFH Y402H genotype in AMD patients and controls from the UK, and response to PDT treatment", Eye (Lond), 22, pp.849~854 (2008)
- Seitsonen SP, "The effect of complement factor H Y402H polymorphism on the outcome of photodynamic therapy in age-related macular degeneration", Eur J Ophthalmol, 17, pp.943~949 (2007)
- Brantley MA Jr, "Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to intravitreal bevacizumab", Ophthalmology, 114, pp.2168~2173 (2007)
- Lee AY, "Pharmacogenetics of complement factor H (Y402H) and treatment of exudative age-related macular degeneration with ranibizumab", Br J Ophthalmol, 93, pp.610~613 (2009)
- Tsuchihashi T, "Complement factor H and high-temperature requirement A-1 genotypes and treatment response of age-related macular degeneration", Ophthalmology, 118, pp.93~100 (2011)
- Sakurada Y, "Association of LOC387715 A69S genotype with visual prognosis after photodynamic therapy for polypoidal choroidal vasculopathy", Retina, 30, pp.1616~1621 (2010)
- Rivera A, "Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk", Hum Mol Genet, 14, pp.3227~3236 (2005)
- De Luca A, "Pattern of expression of HtrA1 during mouse development", J Histochem Cytochem, 52, pp.1609~1617 (2004)
- Oka C, "HtrA1 serine protease inhibits signaling mediated by TGF-beta family proteins", Development, 131, pp.1041~1053 (2004)
- Kaarniranta K, "Heat shock proteins as gatekeepers of proteolytic pathways-Implications for age-related macular degeneration (AMD)", Ageing Res Rev, 8, pp.128~139 (2009)
- Rondanelli M, "Altered oxidative stress in healthy old subjects", Aging (Milano), 9, pp.221~223 (1997)
- Bock F, "Bevacizumab as a potent inhibitor of inflammatory corneal angiogenesis and lymphangiogenesis", Invest Ophthalmol Vis Sci, 48, pp.2545~2552 (2007)
- Spaide RF, "Rationale for combination therapy in age-related macular degeneration", Retina, 29(6 Suppl), pp.5~7 (2009)