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

Purpose To evaluate the association and interaction of five single-nucleotide polymorphisms (SNPs) in three genes ( CFH, ARMS2 , and ARMS2/HTRA1 ) with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in Chinese population. Methods A total of 300 nAMD and 300 PCV patients and 301 normal subjects participated in the present study. The allelic variants of rs800292, rs2274700, rs3750847, rs3793917, and rs1065489 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Gene–gene interactions were evaluated by the data mining approach multifactor-dimensionality reduction (MDR) method. Results The risk alleles of CFH rs800292, rs2274700, ARMS2 rs3057847, and ARMS2/HTRA1 rs3793917 showed significant difference between nAMD or PCV patients and controls (all P <0.01). The homozygosity of risk alleles for rs800292, rs2274700, rs3750847, and rs3793917 were significantly different between nAMD patients and controls (all P <0.01), and predisposed to PCV patients (all P <0.01). After cross-validation consistency (CVC) and permutation tests, the two-locus model rs2274700_rs3750847 has a balanced accuracy of 64.37% in predicting nAMD disease risk. The one-marker model, rs3750847, and two-locus model rs2274700_rs3750847 has a balanced accuracy of 66.07% and 65.89% in predicting PCV disease risk, respectively. Furthermore, CFH rs1065489 did not show significant association with nAMD ( P >0.01), but was strongly associated with PCV in Chinese patients ( P <0.001). Conclusions In this study, we found that the interaction of ARMS2 and ARMS2/HTRA1 is significantly associated with nAMD, and the interaction of CFH and ARMS2 is pronounced in PCV development in Chinese population.