Purpose Genetic factors influence an individual's risk for developing age-related macular degeneration (AMD), a leading cause of irreversible vision loss. Previous studies investigating the potential association between all AMD subtypes and the SERPING1 gene, which encodes a key regulator of the classic complement pathway, have yielded conflicting results. The purpose of this study is to determine whether variations in SERPING1 are associated with neovascular AMD.

Methods A total of 556 patients with neovascular AMD and 256 ethnically matched controls were genotyped for polymorphisms in SERPING1. A tagging single nucleotide polymorphism (tSNP) approach was used to cover the SERPING1 gene plus 2 kb on each side, spanning the promoter and the 3′ untranslated regions. Ten SNPs with a minor allele frequency of 0.10 were covered by three tSNPs (rs1005510, rs11603020, rs2511989).

Results SERPING1 SNPs rs1005510 and rs2511989 were significantly associated with neovascular AMD in our cohort, with rs1005510 conferring an adverse risk effect (OR 1.49, 95% CI 1.18 to 1.88) and rs2511989 conferring a protective effect (OR 0.73, 95% CI 0.59 to 0.90). For both tSNPs, logistic regression of individual genotypes demonstrated statistically significant stepwise changes in the risk of developing AMD. Combined analysis of rs1005510 with variants in CFH and HTRA1 confirmed an independent risk effect. The rs11603020 variant had no effect on AMD susceptibility in this study (OR 0.98, 95% CI 0.78 to 1.24).

Conclusions The SERPING1 gene is comprehensively investigated in this study (using three tSNPs), and its genetic variants are evaluated in the largest neovascular AMD cohort to date. The hypothesis that SERPING1 has a modest effect on the risk of neovascular AMD is supported by our results.