Neovascular AMD and PCV are important macular disorders sharing similar phenotypes and serious clinical complications, including hemorrhagic RPE detachment and vitreous hemorrhage 
, both of which have been used to classify PCV as a subtype of neovascular AMD 
. However, there are discernable differences in their natural courses 
, responses to treatments and overall visual prognosis 
, indicating that PCV could be a type of macular disease that is different from AMD. Based on the reported AMD-associated genes 
, genetic studies have been initiated to investigate the molecular mechanisms underlying the two diseases. Results of genotype analysis, variants at 10q26,have indicated that neovascular AMD and PCV may share common genetic background 
. The associated variants at 10q26 overlap two known genes, PLEKHA1
, and a predicted gene ARMS2
. Each of these can have a plausible biological relationship to macular degeneration 
To clarify the genetic association and evaluate possible mechanism of disease susceptibility, we investigated the genetic profiles of nAMD and PCV through analysis of the ARMS2/HTRA1 locus. A total of 8 polymorphisms in ARMS2 and HTRA1 were found to be associated with both diseases (, , and ). Their genotype frequencies were all significantly different between nAMD and PCV (p<0.05). These results indicate resembling genetic effects in the ARMS2/HTRA1 locus between the two diseases, but the size of the effects were different. Therefore, other genetic variations might also determine the development of exudative AMD and PCV. It is noted that, while the p values and ORs between the individual SNPs with AMD and with PCV may differ, the trend of associations remained the same (, , and ). Therefore, the results showed that nAMD and PCV are subject to the same genetic influence as far as ARMS2 and HTRA1 SNPs are concerned.
In the study reported herein, the significant association was found in rs10490924 and EU427528 (310–311) in the ARMS2. For rs10490924, Our findings suggest risk allele is strongly associated with neovascular AMD and PCV, and with a stronger association in neovascular AMD than in PCV for northern Chinese population. This has been found in Janpanese and Caucasian 
. Meanwhile, the almost same results were presented in EU427528 (310–311). a intron in ARMS2. Some reaseaches have mentioned that this risk allele of TG insertion had a strongly increased risk of developing AMD and PCV 
. Within HTRA1, there was statistical significance in rs55928386 and rs2672598 between AMD patients and controls, but not between PCV patients and controls. Therefore, the two allele had association with AMD, but not with PCV. Our findings also suggest that HTRA1 is involved in nAMD and in PCV for northern Chinese population. In the previous studies for the Japanese population, Kondo and Gotoh found that HTRA1 rs11200638 was significantly associated with PCV and nAMD although the odds ratios were higher for the nAMD cases than the PCV cases in Japanese 
. Lee comparing PCV and controls in Chinese population in Singapore showed rs11200638 to be significantly associated with PCV 
and Liang found ARMS2 in southern Chinese remained significantly associated with AMD but not with PCV 
. However, in our study we found the risk allele was tightly associated with AMD and PCV in northern Chinese population. The different results may be due to the different genetic background between southern and northern Chinese population in mainland China.
Our data indicate that both rs11200638 and rs10490924 share the same LD block which contains ARMS2 and HTRA1. This result is consistent with previous Caucasian studies 
. There is high linkage disequilibrium (LD) across the ARMS2
region, adding to the difficulty in identifying true causal variant(s) by association mapping alone 
. The association signal at 10q26 converges on a region of an extensive LD block spanning ARMS2
. This LD block harbors multiple susceptibility alleles of which the ARMS2
rs10490924 has been reported to show the strongest evidence for association 
. Two variants within this LD block that were correlated with A69S through strong LD–SNP rs11200638 in the promoter of HTRA1 
and the insertion/deletion polymorphism (c.(*)372_815del443ins54) in the 3′-UTR region of ARMS2 
–have recently been proposed as causal variants based on mechanistic functional evidence, but there is no agreement across studies 
. Thus, the molecular basis of the susceptibility remains obscure.
To clarify the plausible biological function of wild-type ARMS2 and ARMS2 A69S mutation in AMD and PCV, we overexpressed these two genes in RF/6A cells and RPE cells as in vitro study model. Our findings showed that compare with wild-type ARMS2, A69S mutation resulted in a significant increase in proliferation and attachment but inhibited cell migration. However, neither wild-type ARMS2 nor A69S mutation affected cell apoptosis. Moreover, we found that neither wild-type ARMS2 nor A69S mutation affected tube formation of RF/6A cells. Tube formation is one of the main characteristics of retinal and choroid vascular endothelial cells, however, A69S mutation overexpressed RF/6A cells showed no significant difference with wild-type ARMS2 overexpressed ones on tubule formation. Therefore, neither wild-type ARMS2 nor A69S mutation might play a role in maintaining the tube-forming properties of RF/6A cells. Therefore, we thought neither wild-type ARMS2 nor A69S mutation had direct association with neovascularisation in the pathogenesis of AMD, which can explained ARMS2 has a significant association with pure dry AMD 
. Although we cannot formally reject the hypothesis that loss of LOC387715 is irrelevant to the disease, the spatiotemporal expression pattern of this gene and its exclusive emergence with the evolution of the macula in non-human primates, provide partial evidence for its role in AMD pathogenesis. We must note that AMD is a multifactorial disease with numerous susceptibility loci, therefore, the altered ARMS2 expression or function alone will not be sufficient to cause AMD.