Genotypes of SNPs of Key Genes Regulate Susceptibility and Drug Sensitivity to Neovascular AMD

<p>Age-related macular degeneration (AMD), particularly its neovascular form, stands as a leading cause of blindness globally, with its prevalence in our country on a steady rise. This underscores the critical impact of neovascular AMD (nAMD) management on patient quality of life and societal burden. Current optimal treatments hinge on anti-vascular endothelial growth factor (anti-VEGF) therapies, though their efficacy varies across different drugs and individuals, highlighting the importance of precise drug selection in clinical outcomes. Research suggests that factors such as baseline vision, age, disease duration, lesion size, central retina thickness, neovascularization type, and demographic differences influence nAMD prognosis. In addition, Genetic predispositions and environmental factors also contribute to nAMD development, with increasing focus on molecular genetics to understand treatment responses. Single nucleotide polymorphisms (SNPs), as primary genomic variations, are linked to disease susceptibility and treatment sensitivity, including in nAMD. This study posits that SNP interactions within human genes may influence anti-VEGF drug’s efficacy, supported by evidence on the distinct molecular functions and pathways of VEGF family genes. We aimed to analyze nAMD susceptibility and sensitivity to VEGF inhibitors and explore gene polymorphisms at the molecular level, demonstrating that SNP presence could elucidate variances in anti-VEGF drug performance, thereby optimizing clinical drug selection and minimizing treatment failures. Given the high costs associated with anti-VEGF therapies, adopting a precision medicine approach, guided by genetic insights, is crucial for economic and clinical efficiency. This study provides a foundation for personalized treatment strategies, efficacy monitoring, individual variability assessment, biologic development, and etiological analysis in nAMD management. We investigated the presence of SNPs in nAMD patients, examining the correlation between gene SNPs, genetic susceptibility, and anti-VEGF drug efficacy. Selecting 30 SNP sites from 14 genes associated with nAMD, we analyzed their contribution to disease occurrence and treatment response, revealing significant SNP-related individual differences in drug sensitivity and cross-efficacy. Our research encompasses three main aspects: firstly, reviewing pathogenic factors of nAMD and anti-VEGF drug effects; secondly, conducting a retrospective study comparing the effectiveness and safety of conbercept and ranibizumab; thirdly, analyzing the association between gene SNPs and nAMD etiology and drug efficacy. Significant genotype differences were found, underscoring the potential of genotype-based personalized treatments for enhanced clinical outcomes in nAMD management.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biomedical Sciences

Year dc:date.available

2024

Author dc:creator

• Cui, Jinglin

Contributors dc:contributor

• Weikuan Gu, PhD

• Choroidal Neovascularization
• KH902 fusion protein
• Macular Degeneration
• Polymorphism Single Nucleotide
• Ranibizumab
• Vascular Endothelial Growth Factor A
• Diseases
• Eye Diseases
• Geriatrics
• Medical Genetics
• Medicine and Health Sciences
• Ophthalmology
• Therapeutics

Repository record dc:identifier

https://dc.uthsc.edu/dissertations/690

OAI identifier oai:identifier

oai:dc.uthsc.edu:dissertations-1690