Abstract
Purpose:
To investigate gene polymorphisms in the complement pathway (the C2-CFB-RDBP-SKIV2L locus, SERPING1, C3, C5 and C7) in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV).
Methods:
Haplotype-tagging SNPs in the 5 genetic loci were genotyped in a Hong Kong Chinese cohort of 200 neovascular AMD patients, 250 PCV patients and 300 control subjects, by using TagMan genotyping technology.
Results:
We found SKIV2L, but not C2/CFB, responsible for the global association of the C2-CFB-RDBP-SKIV2L locus with neovascular AMD. The association of SKIV2L rs429608 remained significant (P<0.001, OR=0.22) after adjusting for CFH rs800292 and HTRA1 rs11200638. No individual SNP or haplotype in this locus was associated with PCV. C3 rs17030 was associated with PCV (p<0.01, OR=2.94) but not AMD, and showed a male-specific association in PCV (p<0.05). No SNPs in C5 and C7 were associated with AMD or PCV. But significant SNP-SNP interactions were identified between C5 and C3 for neovascular AMD (C5-rs2269066 and C3-rs2230205, p<0.01) and for PCV (C5-rs2269066 and C3-rs2230205, p<0.01; C5-rs1548782 and C3-rs2250656, p<0.01). Also we found no SERPING1 SNPs associated with PCV or AMD in our Chinese cohort, but a meta-analysis revealed the association of rs2511989 with AMD in Caucasians.
Conclusions:
Neovascular AMD and PCV in our Chinese cohort have consistently significant or insignificant associations with SERPING1, C5 and C7, but different association patterns on the C2-CFB-RDBP-SKIV2L locus and C3.
Keywords: 412 age-related macular degeneration