Pharmacogenetic research aims to examine and identify genetic factors related to treatment responsiveness to drugs and side effects. There are>50 reports examining the relationship between responsiveness to vascular endothelial growth factor (VEGF) treatment for age-related macular degeneration (AMD) and genetic factors, but comprehensive studies are limited. To search for genetic factors associated with visual outcome in anti-VEGF treatment for AMD, We conducted a genome-wide association study (GWAS) including 919 AMD patients treated at seven centers in Japan. The results revealed that single-nucleotide polymorphisms (SNPs) satisfying the genome-wide significance level were not identified; however, the associations of four SNPs were suggested. We constructed a risk score model using clinical items and four SNPs and examined the predictive ability. By adding four SNPs to clinical items (i. e., age, visual acuity at the baseline, and past treatment history), the area under the receiver operating characteristic (ROC) curve significantly improved from 0.61 to 0.71. Although no genetic marker to predict responses to anti-VEGF therapy has been identified, replication study for previously suggested SNPs and meta-GWAS in collaboration with research groups are warranted to achieve personalized medicine for AMD patients.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 124: 853-860, 2020.