Genotypes of SNPs of key genes regulate susceptibility and drug sensitivity to neovascular AMD in the human population
Objective To compare the genetic characteristics of the normal control group to those of neovascular age-related macular degeneration (AMD) patients and to detect single-nucleotide polymorphisms (SNPs) related to the pathogenesis of neovascular AMD and the sensitivity to anti-VEGF drug, combercept.M...
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BMJ Publishing Group
2025-04-01
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| Series: | BMJ Open Ophthalmology |
| Online Access: | https://bmjophth.bmj.com/content/10/1/e001872.full |
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| author | Boyang Liu Lu Lu Zhuo Li Hang Lu Baofeng Yang Dawei Sun Weikuan Gu Anqi Zhao Jinglin Cui Suoxi Wang Xiande Song Weiwei Xiu Jiayao Li Chaoming Jin Hongyang Ding Monica M Jablonski |
| author_facet | Boyang Liu Lu Lu Zhuo Li Hang Lu Baofeng Yang Dawei Sun Weikuan Gu Anqi Zhao Jinglin Cui Suoxi Wang Xiande Song Weiwei Xiu Jiayao Li Chaoming Jin Hongyang Ding Monica M Jablonski |
| author_sort | Boyang Liu |
| collection | DOAJ |
| description | Objective To compare the genetic characteristics of the normal control group to those of neovascular age-related macular degeneration (AMD) patients and to detect single-nucleotide polymorphisms (SNPs) related to the pathogenesis of neovascular AMD and the sensitivity to anti-VEGF drug, combercept.Method This is a prospective case-controlled study. A total of 104 neovascular AMD patients were treated with combercept and 106 normal subjects were served as the control group. SNPs associated with neovascular AMD and disease susceptibility and drug sensitivity were analysed.Results Significant differences existed between neovascular AMD patients and normal subjects among genotypes of the SNPs of two genes, ARMS2 (rs10490924 T) and HTRA 1 (rs11200638 A). The T alleles in rs1065489 of CFH and the rs2230205 of C3 significantly promoted neovascular AMD in males while having no significant effect in females. Six SNPs of five genes, including C3 (rs2250656 G), CFB (rs2072633 G), CFH (rs2274700 A, rs3766405 T), KDR (rs6828477 A) and FZD 4 (rs10898563 T), had significant impact in reducing neovascular AMD. Two SNPs of the CFH gene (rs2274700 A and rs3766405 T) and one SNP of the CFB gene, rs2072633 G, were statistically significantly associated with good response to combercept. Conversely, the other two SNPs of the CFH gene, rs1065489 T and rs3753396 G, and the rs7412 T of the APOE gene were associated with a relatively poor patient response to drug action. Two sets of SNPs of CFB have a combined positive effect on disease. The two SNPs of CFH (rs1065489 T and rs3753396 G) and the combination of the two SNPs of CFH and rs7412T of APOE have negative effects on the drug effectiveness.Conclusions These genotype differences facilitate the selection of individualised treatment options towards obtaining the most efficacious clinical treatment. These findings need to be validated by studies with different ethnic populations and/or larger samples. |
| format | Article |
| id | doaj-art-1a36d75a77f84c26b0394da642488bfc |
| institution | DOAJ |
| issn | 2397-3269 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open Ophthalmology |
| spelling | doaj-art-1a36d75a77f84c26b0394da642488bfc2025-08-20T03:09:00ZengBMJ Publishing GroupBMJ Open Ophthalmology2397-32692025-04-0110110.1136/bmjophth-2024-001872Genotypes of SNPs of key genes regulate susceptibility and drug sensitivity to neovascular AMD in the human populationBoyang Liu0Lu Lu1Zhuo Li2Hang Lu3Baofeng Yang4Dawei Sun5Weikuan Gu6Anqi Zhao7Jinglin Cui8Suoxi Wang9Xiande Song10Weiwei Xiu11Jiayao Li12Chaoming Jin13Hongyang Ding14Monica M Jablonski15Department of Ophthalmology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, ChinaDepartment of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee, USADepartment of Ophthalmology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, ChinaDepartment of Ophthalmology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, ChinaDepartment of Pharmacology, Ministry of Education, Brasilia, BrazilDepartment of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, ChinaDepartment of Orthopedic Surgery, The University of Tennessee Health Science Center, Memphis, Tennessee, USADepartment of Ophthalmology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, ChinaDepartment of Ophthalmology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, ChinaDepartment of Ophthalmology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, ChinaDepartment of Ophthalmology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, ChinaDepartment of Ophthalmology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, ChinaMudanjiang Medical University, Mudanjiang, Heilongjiang, ChinaMudanjiang Medical University, Mudanjiang, Heilongjiang, ChinaDepartment of Ophthalmology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, ChinaDepartment of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, USAObjective To compare the genetic characteristics of the normal control group to those of neovascular age-related macular degeneration (AMD) patients and to detect single-nucleotide polymorphisms (SNPs) related to the pathogenesis of neovascular AMD and the sensitivity to anti-VEGF drug, combercept.Method This is a prospective case-controlled study. A total of 104 neovascular AMD patients were treated with combercept and 106 normal subjects were served as the control group. SNPs associated with neovascular AMD and disease susceptibility and drug sensitivity were analysed.Results Significant differences existed between neovascular AMD patients and normal subjects among genotypes of the SNPs of two genes, ARMS2 (rs10490924 T) and HTRA 1 (rs11200638 A). The T alleles in rs1065489 of CFH and the rs2230205 of C3 significantly promoted neovascular AMD in males while having no significant effect in females. Six SNPs of five genes, including C3 (rs2250656 G), CFB (rs2072633 G), CFH (rs2274700 A, rs3766405 T), KDR (rs6828477 A) and FZD 4 (rs10898563 T), had significant impact in reducing neovascular AMD. Two SNPs of the CFH gene (rs2274700 A and rs3766405 T) and one SNP of the CFB gene, rs2072633 G, were statistically significantly associated with good response to combercept. Conversely, the other two SNPs of the CFH gene, rs1065489 T and rs3753396 G, and the rs7412 T of the APOE gene were associated with a relatively poor patient response to drug action. Two sets of SNPs of CFB have a combined positive effect on disease. The two SNPs of CFH (rs1065489 T and rs3753396 G) and the combination of the two SNPs of CFH and rs7412T of APOE have negative effects on the drug effectiveness.Conclusions These genotype differences facilitate the selection of individualised treatment options towards obtaining the most efficacious clinical treatment. These findings need to be validated by studies with different ethnic populations and/or larger samples.https://bmjophth.bmj.com/content/10/1/e001872.full |
| spellingShingle | Boyang Liu Lu Lu Zhuo Li Hang Lu Baofeng Yang Dawei Sun Weikuan Gu Anqi Zhao Jinglin Cui Suoxi Wang Xiande Song Weiwei Xiu Jiayao Li Chaoming Jin Hongyang Ding Monica M Jablonski Genotypes of SNPs of key genes regulate susceptibility and drug sensitivity to neovascular AMD in the human population BMJ Open Ophthalmology |
| title | Genotypes of SNPs of key genes regulate susceptibility and drug sensitivity to neovascular AMD in the human population |
| title_full | Genotypes of SNPs of key genes regulate susceptibility and drug sensitivity to neovascular AMD in the human population |
| title_fullStr | Genotypes of SNPs of key genes regulate susceptibility and drug sensitivity to neovascular AMD in the human population |
| title_full_unstemmed | Genotypes of SNPs of key genes regulate susceptibility and drug sensitivity to neovascular AMD in the human population |
| title_short | Genotypes of SNPs of key genes regulate susceptibility and drug sensitivity to neovascular AMD in the human population |
| title_sort | genotypes of snps of key genes regulate susceptibility and drug sensitivity to neovascular amd in the human population |
| url | https://bmjophth.bmj.com/content/10/1/e001872.full |
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