With meta-analyses, variants in four genes were found to be significantly associated with PCV: LOC387715 rs10490924 (n=9, allelic odds ratio [OR]=2.27, p<0.00001), HTRA1rs11200638 (n=4, OR=2.72, p<0.00001), CFH rs1061170 (n=4, OR=1.72, p<0.00001), CFH rs800292 (n=5, OR=2.10, p<0.00001), and C2 rs547154 (n=3, OR=0.56, p=0.01).
The decreased biological function of vascular endothelial cells and the degradation of extracellular matrix proteins, such as fibronectin, may be involved in a contributory role for HTRA1 in PCV pathogenesis.
The association pattern and haplotype estimation in the ARMS2/HTRA1 region of Japanese patients with PCV were very similar to those of Japanese patients with typical nAMD.
Significant associations with both nAMD and PCV were observed in 2 polymorphisms of ARMS2 and HTRA1rs11200638, with different genotypic distributions between nAMD and PCV (p<0.001).
Gene-gene interaction of CFH, ARMS2, and ARMS2/HTRA1 on the risk of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in Chinese population.
Weaker association for PCV was observed at ARMS2-HTRA1 (P<sub>dif</sub>=4.39 × 10<sup>-4</sup>) and KMT2E-SRPK2(P<sub>dif</sub>=4.43 × 10<sup>-3</sup>), compared with tAMD.
The variants in CFH, ARMS2 and near HTRA1 were strongly associated with both PCV (P < 10(-6), 10(-7) and 10(-7) respectively) and nAMD (P < 10(-6), 10(-16) and 10(-17) respectively).
There is a strong and consistent association of the ARMS2/HTRA1 locus with both exudative AMD and PCV, suggesting the two disorders share, at least partially, similar molecular mechanisms.
There was no significant difference in the incidence of CFH Y402H (P = 0.598) and HTRA1rs11200638 (P = 0.290) between eyes with typical exudative AMD and with PCV.
Intravitreal delivery of an HTRA1 inhibitor (DPMFKLboroV) was effective (36% lesion reduction; P = 0.009) in preventing PCV initiation but ineffective in treating existing lesions.
Four AMD-associated haplotype-tagging alleles (rs547154, rs1061170, rs1410996, rs10490924) in the 3 major loci, CFH, CFB/C2, and ARMS2/HTRA1, also were statistically significantly associated with the PCV phenotype (P<0.05).