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

Authors

  • Nur Afiqah Mohamad Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia
  • Vasudevan Ramachandran Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia
  • Patimah Ismail Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia
  • Hazlita Mohd Isa Department of Ophthalmology, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia
  • Yoke Mun Chan Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia
  • Nor Fariza Ngah Department of Ophthalmology, Hospital Selayang, Lebuhraya Selayang - Kepong, Batu Caves, Malaysia
  • Norshakimah Md Bakri Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia
  • Siew Mooi Ching Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia
  • Fan Kee Hoo Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia
  • Wan Aliaa Wan Sulaiman Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia
  • Liyana Najwa Inche Mat Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia
  • Mohd Hazmi Mohamed Department of Surgery, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia

DOI:

https://doi.org/10.17305/bjbms.2018.2493

Keywords:

Age-related macular degeneration, AMD, complement factor H, CFH, ranibizumab, Y402H, SNP, treatment response

Abstract

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.

Author Biographies

  • Patimah Ismail, Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia
    Department of Biomedical Science
  • Hazlita Mohd Isa, Department of Ophthalmology, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia
    Department of Ophthalmology
  • Yoke Mun Chan, Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia
    Department of Nutrition and Dietetics
  • Nor Fariza Ngah, Department of Ophthalmology, Hospital Selayang, Lebuhraya Selayang - Kepong, Batu Caves, Malaysia
    Department of Ophthalmology
  • Siew Mooi Ching, Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia
    Department of Family Medicine
  • Fan Kee Hoo, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia
    Department of Medicine
  • Wan Aliaa Wan Sulaiman, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia
    Department of Medicine
  • Liyana Najwa Inche Mat, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia
    Department of Medicine
  • Mohd Hazmi Mohamed, Department of Surgery, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor DE, Malaysia
    Department of Surgery

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

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01-08-2018

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1.
Analysis of the association between CFH Y402H polymorphism and response to intravitreal ranibizumab in patients with neovascular age-related macular degeneration (nAMD). Biomol Biomed [Internet]. 2018 Aug. 1 [cited 2024 Mar. 29];18(3):260-7. Available from: https://bjbms.org/ojs/index.php/bjbms/article/view/2493