Effect of VEGF-A gene mutation on neovascular age-related macular degeneration and the response to ranibizumab

Authors: Song Shuang,  Yang Fan,  Gu Xiaoya,  Zhang Peng,  Yu Xiaobing,  Dai Hong

DOI: 10.3760/cma.j.cn115989-20200509-00320
Published 2020-08-10
Cite as Chin J Exp Ophthalmol, 2020,38(08): 680-685.

Abstract

Objective

To investigate the effect of vascular endothelial growth factor-A (VEGFA) gene mutation to neovascular age-related macular degeneration (nAMD) and the response to ranibizumab with this mutation in Chinese.

Methods

This was a case-control study.We recruited 127 cases (diagnosed as nAMD) and 101 ethical, age and geographical area matched unrelated healthy controls in Beijing Hospital from February 2017 to January 2018.The patients with nAMD were divided into two subgroups: good response to intravitreal ranibizumab (IVR) and poor response to IVR based on whether gain 5 letters 3 months after therapy.Phenol chloroform method was used in purification of genomic DNA in the peripheral venous blood of each individual.All exons and 2 kb upstream and downstream sequence of VEGF-A was sequenced by using Sanger Sequenced method, and candidate variations were screened out.Restriction fragment length polymorphism (RFLP) method was used in genotyping of the case-control study.Hardy-Weinberg equilibrium was used to test the representativeness of the sample group.The differences of allele distribution frequency and genotype distribution frequency between the case group and control group, good response group and poor response group were compared.Written informed consent was obtained from each subject prior to entering the study cohort.The study protocol was approved by the Ethics Committee of Beijing Hospital (No.2017S-012).

Results

The mutation (rs3025018) was located in 7th intron of VEGF-A.The allele were C, G, T and the genotype were CC, CT, CG, TT and TG.The allele distribution frequency between the case and control group were significantly different (χ2=7.492, P=0.024). The allele G vs. C+ T distribution frequency between the case and control group were significantly different (χ2=7.490, P=0.006). The genotype distribution frequency between the case group and control group were significantly different (χ2=13.376, P=0.010). The genotype (CG+ GT vs. CC+ CT+ TT) distribution frequency between the case group and control group were significantly different (χ2=8.335, P=0.004). The allele frequencies or genotype frequency were not significantly different between the good response group and poor response group (all at P>0.05).

Conclusions

G allele of VEGFA (rs3025018) carriers were less possible to occur nAMD compared with C and T allele.However, there is no effect of VEGFA gene mutations (rs3025018) on response to ranibizumab for nAMD.

Key words:

Age-related macular degeneration; Vascular endothelial growth factor-A; Mutation; Ranibizumab

Contributor Information

Song Shuang
Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
Yang Fan
Shanghai Institute of Medical Genetics, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Key Laboratory of Embryo Molecular Biology, Ministry of Health & Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai 200040, China
Gu Xiaoya
Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
Zhang Peng
Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
Yu Xiaobing
Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
Dai Hong
Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
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Updated: August 19, 2020 — 9:05 am