Association of IGFN1 variant with polypoidal choroidal vasculopathy

Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (nAMD) share a similar phenotype but are different in their clinical manifestations, responses to treatment and prognosis. Whether PCV is a subtype of AMD or a distinct entity from nAMD remains unknown. Therefore, we performed a whole-exome sequencing based association analysis to compare the genetic architecture of PCV and nAMD in Han Chinese.

Whole-exome sequencing analysis was performed on 21 nAMD cases, 20 PCV cases and 20 healthy controls. As a follow-up validation, 145 nAMD cases, 160 PCV cases and 193 controls were genotyped using the Sequenom MassARRAY platform (Sequenom, San Diego, CA, USA).

A novel variant, c.6196A>G in the IGFN1 gene, was significantly associated with only PCV (combined p = 7.1 × 10^-11 , odds ratio = 9.44), but not with nAMD (combined p = 0.683, odds ratio = 1.30). The minor allele G conferred an increased risk of PCV.

The findings of the present study indicate that, although some of the susceptibility loci are shared between PCV and nAMD, a unique genetic signature may decide the pathogenesis of PCV.