Genome-wide association study of the response of patients with diabetic macular edema to intravitreal Anti-VEGF injection
Abstract Diabetic macular edema (DME), a complication of diabetes mellitus, is a leading cause of adult-onset blindness worldwide. Recently, intravitreal anti-VEGF injection has been used as a first-line treatment. This study analyzed the association between the genetic profile of patients with DME...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-12-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-26048-7 |
| _version_ | 1797973610098327552 |
|---|---|
| author | Eun Hee Hong Hoseok Yeom Hyo Seon Yu Jong Eun Park Yong Un Shin So-Young Bang Heeyoon Cho |
| author_facet | Eun Hee Hong Hoseok Yeom Hyo Seon Yu Jong Eun Park Yong Un Shin So-Young Bang Heeyoon Cho |
| author_sort | Eun Hee Hong |
| collection | DOAJ |
| description | Abstract Diabetic macular edema (DME), a complication of diabetes mellitus, is a leading cause of adult-onset blindness worldwide. Recently, intravitreal anti-VEGF injection has been used as a first-line treatment. This study analyzed the association between the genetic profile of patients with DME and their response to treatment. Intravitreal anti-VEGF injections were administered monthly for three months to Korean patients diagnosed with DME, who were classified into two groups depending on whether they responded to anti-VEGF therapy or showed recurrence within six months. Peripheral blood samples were used for genetic analyses. Genome-wide association analysis results sowed that the genes DIRC3 on chromosome 2 (rs16857280, p = 1.2 × 10–6), SLCO3A1 on chromosome 15 (rs12899055, p = 2.5 × 10–6), and RAB2A on chromosome 8 (rs2272620, p = 4.6 × 10–6) were associated with treatment response to intravitreal anti-VEGF injection. SLC35F1, TMEM132D, KIAA0368, HPCAL1, IGF2BP3, SPN2S, COL23A1, and CREB5 were also related to treatment response (p < 5.0 × 10–5). Using the KEGG pathway analysis, RAB2A and CREB5 were found to be associated with AMPK signaling related to VEGF (p = 0.018). The identified genetic biomarkers can elucidate the factors affecting patient response to intravitreal anti-VEGF injection and help select appropriate therapeutic strategy. |
| first_indexed | 2024-04-11T04:07:00Z |
| format | Article |
| id | doaj.art-0ad63ea039144a1cacb789e10b696b90 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T04:07:00Z |
| publishDate | 2022-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0ad63ea039144a1cacb789e10b696b902023-01-01T12:17:26ZengNature PortfolioScientific Reports2045-23222022-12-011211910.1038/s41598-022-26048-7Genome-wide association study of the response of patients with diabetic macular edema to intravitreal Anti-VEGF injectionEun Hee Hong0Hoseok Yeom1Hyo Seon Yu2Jong Eun Park3Yong Un Shin4So-Young Bang5Heeyoon Cho6Department of Ophthalmology, Hanyang University College of MedicineDepartment of Ophthalmology, Asan Medical Center, University of Ulsan College of MedicineDepartment of Ophthalmology, Hanyang University College of MedicineDepartment of Laboratory Medicine, Hanyang University Guri Hospital, Hanyang University College of MedicineDepartment of Ophthalmology, Hanyang University College of MedicineDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Ophthalmology, Hanyang University College of MedicineAbstract Diabetic macular edema (DME), a complication of diabetes mellitus, is a leading cause of adult-onset blindness worldwide. Recently, intravitreal anti-VEGF injection has been used as a first-line treatment. This study analyzed the association between the genetic profile of patients with DME and their response to treatment. Intravitreal anti-VEGF injections were administered monthly for three months to Korean patients diagnosed with DME, who were classified into two groups depending on whether they responded to anti-VEGF therapy or showed recurrence within six months. Peripheral blood samples were used for genetic analyses. Genome-wide association analysis results sowed that the genes DIRC3 on chromosome 2 (rs16857280, p = 1.2 × 10–6), SLCO3A1 on chromosome 15 (rs12899055, p = 2.5 × 10–6), and RAB2A on chromosome 8 (rs2272620, p = 4.6 × 10–6) were associated with treatment response to intravitreal anti-VEGF injection. SLC35F1, TMEM132D, KIAA0368, HPCAL1, IGF2BP3, SPN2S, COL23A1, and CREB5 were also related to treatment response (p < 5.0 × 10–5). Using the KEGG pathway analysis, RAB2A and CREB5 were found to be associated with AMPK signaling related to VEGF (p = 0.018). The identified genetic biomarkers can elucidate the factors affecting patient response to intravitreal anti-VEGF injection and help select appropriate therapeutic strategy.https://doi.org/10.1038/s41598-022-26048-7 |
| spellingShingle | Eun Hee Hong Hoseok Yeom Hyo Seon Yu Jong Eun Park Yong Un Shin So-Young Bang Heeyoon Cho Genome-wide association study of the response of patients with diabetic macular edema to intravitreal Anti-VEGF injection Scientific Reports |
| title | Genome-wide association study of the response of patients with diabetic macular edema to intravitreal Anti-VEGF injection |
| title_full | Genome-wide association study of the response of patients with diabetic macular edema to intravitreal Anti-VEGF injection |
| title_fullStr | Genome-wide association study of the response of patients with diabetic macular edema to intravitreal Anti-VEGF injection |
| title_full_unstemmed | Genome-wide association study of the response of patients with diabetic macular edema to intravitreal Anti-VEGF injection |
| title_short | Genome-wide association study of the response of patients with diabetic macular edema to intravitreal Anti-VEGF injection |
| title_sort | genome wide association study of the response of patients with diabetic macular edema to intravitreal anti vegf injection |
| url | https://doi.org/10.1038/s41598-022-26048-7 |
| work_keys_str_mv | AT eunheehong genomewideassociationstudyoftheresponseofpatientswithdiabeticmacularedematointravitrealantivegfinjection AT hoseokyeom genomewideassociationstudyoftheresponseofpatientswithdiabeticmacularedematointravitrealantivegfinjection AT hyoseonyu genomewideassociationstudyoftheresponseofpatientswithdiabeticmacularedematointravitrealantivegfinjection AT jongeunpark genomewideassociationstudyoftheresponseofpatientswithdiabeticmacularedematointravitrealantivegfinjection AT yongunshin genomewideassociationstudyoftheresponseofpatientswithdiabeticmacularedematointravitrealantivegfinjection AT soyoungbang genomewideassociationstudyoftheresponseofpatientswithdiabeticmacularedematointravitrealantivegfinjection AT heeyooncho genomewideassociationstudyoftheresponseofpatientswithdiabeticmacularedematointravitrealantivegfinjection |