Genome-wide association study of the response of patients with diabetic macular edema to intravitreal Anti-VEGF injection

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=1.2x10(-6)), SLCO3A1 on chromosome 15 (rs12899055, p=2.5x10(-6)), and RAB2A on chromosome 8 (rs2272620, p=4.6x10(-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<5.0x10(-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.

Automated summary

This study analyzed the association between the genetic profile of patients with diabetic macular edema (DME) and their response to intravitreal anti-VEGF injection. Several genes were found to be associated with treatment response, including DIRC3, SLCO3A1, and RAB2A. Pathway analysis revealed a connection between RAB2A and CREB5 with AMPK signaling related to VEGF. These genetic biomarkers can provide insights into patient response and guide therapeutic strategies.