To investigate whether the LOC387715/ARMS2 variants are associated with an angiographic phenotype, including lesion size and composition, in subfoveal polypoidal choroidal vasculopathy.
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).
To compare the genomic contribution of the ARMS2/HTRA1 region of chromosome 10q26 to typical neovascular age-related macular degeneration (nAMD) (also known as typical exudative AMD) and to polypoidal choroidal vasculopathy (PCV) METHODS: DNA samples were prepared from 84 patients with typical nAMD, 181 patients with PCV, and 276 control participants.
Although there was no association of CFH I62V variants with any of the phenotypes in PCV, at-risk variants of ARMS2A69S were associated with higher incidences of subretinal hemorrhage, serous PED, and hemorrhagic PED.
Severe vision-threatening complications (ie, suprachoroidal hemorrhage, vitreous hemorrhage, and tears of the retinal pigment epithelium) were seen only in eyes with larger PCV, and in studying single nucleotide polymorphisms A69S of ARMS2 genes, there was a significant difference in T allele frequency between individuals with smaller PCV and those with larger PCV (20.2% vs 79.8%; P = .0235).
rs800292" genes_norm="3075">I62V (rs800292) in the CFH gene and A69S (rs10490924) in the ARMS2 gene were genotyped, and case-control studies were performed in subjects with these PCV subtypes.
Results were then integrated into a meta-analysis of previous studies representing an assessment of the association between the ARMS2A69S variant and neovascular AMD and/or PCV, comprising a total of 3,828 subjects of Asian descent.
Furthermore, an independent association of C2/CFB variants was found for both typical AMD and PCV with age, sex, smoking, and genetic background of ARMS2A69S and CFH I62V (vs. typical AMD: P = 0.0073, odds ratio [OR] = 0.47; vs. PCV: P = 0.0083, OR = 0.53).
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).
After adjusting for age, gender, ARMS2A69S, and CFHI62V, the A allele of rs429608 was significantly protective against neovascular AMD (odds ratio [OR] 0.24, 95% confidence interval [CI] 0.122-0.484, p < 0.001), PCV (OR 0.43, 95% CI 0.262-0.704, p = 0.001), RAP (OR 0.09, 95% CI 0.014-0.581, p = 0.011).
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.
Subfoveal choroidal thickness and CVH in eyes with treatment-naive polypoidal choroidal vasculopathy were associated with ARMS2rs10490924" genes_norm="387715">A69S (rs10490924) and CFH (rs1329428).