Analysis of the association between CFH Y402H polymorphism and response to intravitreal ranibizumab in patients with neovascular age-related macular degeneration (nAMD)

被引:7
作者
Mohamad, Nur Afiqah [1 ]
Ramachandran, Vasudevan [1 ]
Ismail, Patimah [2 ]
Isa, Hazlita Mohd [3 ]
Chan, Yoke Mun [1 ,4 ]
Ngah, Nor Fariza [5 ]
Bakri, Norshakimah Md [1 ]
Ching, Siew Mooi [6 ]
Hoo, Fan Kee [7 ]
Sulaiman, Wan Aliaa Wan [7 ]
Mat, Liyana Najwa Inche [7 ]
Mohamed, Mohd Hazmi [8 ]
机构
[1] Univ Putra Malaysia, Malaysian Res Inst Ageing, Serdang 43400, Selangor De, Malaysia
[2] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Biomed Sci, Serdang, Selangor De, Malaysia
[3] Univ Kebangsaan Malaysia, Med Ctr, Dept Ophthalmol, Kuala Lumpur, Malaysia
[4] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Nutr & Dietet, Serdang, Selangor De, Malaysia
[5] Hosp Selayang, Dept Ophthalmol, Lebuhraya Selayang Kepon, Malaysia
[6] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Family Med, Serdang, Selangor De, Malaysia
[7] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Med, Serdang, Selangor De, Malaysia
[8] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Surg, Serdang, Selangor De, Malaysia
关键词
Age-related macular degeneration; AMD; complement factor H; CFH; ranibizumab; Y402H; SNP; treatment response; COMPLEMENT FACTOR-H; GENETIC ASSOCIATION; PHARMACOGENETICS; AMD; POPULATION; BEVACIZUMAB; THERAPY; VARIANT; RISK;
D O I
10.17305/bjbms.2018.2493
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Pharmacogenetic studies indicate that a variable response to anti-vascular endothelial growth factor (VEGF) therapy in patients with neovascular form of AMD (nAMD) may be due to polymorphisms in the complement factor H gene (CFH). This study is the first to investigate the association between CFH Y402H polymorphism and the response to ranibizumab therapy in Malaysian patients with nAMD. We included 134 patients with nAMD, examined between September 2014 and February 2016. The diagnosis of nAMD was confirmed by ophthalmologic examination, before ranibizumab therapy was started. Each patient received an intravitreal injection of 0.5 mg/0.05 ml ranibizumab following a treat-and-extend (TE) regimen. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded after 3 and 6 months following the first injection and compared with the baseline values. Genotyping of Y402H (rs1061170) polymorphism was performed using PCR-RFLP and the amplified product was digested with MluCI restriction enzyme. Association between the Y402H genotypes and response to treatment was determined by a logistic regression analysis of responder (n = 49) and non-responder (n = 84) group. Significantly worse mean BCVA was observed for the CC genotype compared to the TT + CT genotype in the total sample after 6-month follow-up (p = 0.018). Comparing the baseline and 6-month point measurements, improved mean BCVA was observed in responder group, while worse mean BCVA was recorded for non-responder group. However, our regression analysis, adjusted for confounding factors, showed no significant association between the Y402H genotypes and response to treatment in nAMD patients under the recessive model (p > 0.05). Overall, our results suggest that factors other than Y402H polymorphism may be involved in the progression of nAMD after treatment with anti-VEGF agents, in Malaysian population.
引用
收藏
页码:260 / 267
页数:8
相关论文
共 34 条
[1]  
Anand R, 2000, OPHTHALMOLOGY, V107, P2224
[2]   Analysis of the Y402H variant of the complement factor H gene in age-related macular degeneration [J].
Baird, Paul N. ;
Islam, F. M. Amirul ;
Richardson, Andrea J. ;
Cain, Melinda ;
Hunt, Nicola ;
Guymer, Robyn .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2006, 47 (10) :4194-4198
[3]   Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to intravitreal bevacizumab [J].
Brantley, Milam A., Jr. ;
Fang, Amy M. ;
King, Jennifer M. ;
Tewari, Asheesh ;
Kymes, Steven M. ;
Shiels, Alan .
OPHTHALMOLOGY, 2007, 114 (12) :2168-2173
[4]   Ranibizumab versus Verteporfin Photodynamic Therapy for Neovascular Age-Related Macular Degeneration: Two-Year Results of the ANCHOR Study [J].
Brown, David M. ;
Michels, Mark ;
Kaiser, Peter K. ;
Heier, Jeffrey S. ;
Sy, Judy P. ;
Ianchulev, Tsontcho .
OPHTHALMOLOGY, 2009, 116 (01) :57-65
[5]  
Chan WM, 2016, HONG KONG J OPHTHALM, V14, P14
[6]  
Chang W, 2013, MOL VIS, V19, P702
[7]   Pharmacogenetics of Complement Factor H Y402H Polymorphism and Treatment of Neovascular AMD with Anti-VEGF Agents: A Meta-Analysis [J].
Chen, Guohai ;
Tzekov, Radouil ;
Li, Wensheng ;
Jiang, Fangzheng ;
Mao, Sihong ;
Tong, Yuhua .
SCIENTIFIC REPORTS, 2015, 5
[8]  
Dikmetas O, 2013, MOL VIS, V19, P2571
[9]  
Francis Peter James, 2011, Trans Am Ophthalmol Soc, V109, P115
[10]  
Friedman DS, 2004, ARCH OPHTHALMOL-CHIC, V122, P532