Complement Factor H and Complement Component 2 Polymorphisms in Chinese Patients With Idiopathic Polypoidal Choroidal Vasculopathy

Abstract

Purpose:: Idiopathic polypoidal choroidal vasculopathy (IPCV) is a major cause of serosanguinous maculopathy in Chinese patients with age-related macular degeneration (AMD) and can lead to irreversible visual loss and blindness. Recent studies have shown a strong association of the Y402H polymorphism in complement factor H gene (CFH) in Caucasians and recently in Taiwanese Chinese patients with neovascular AMD. The E318D variant of complement component 2 (C2) was found to confer a significantly reduced risk of AMD in Caucasians. Our aim is to investigate if these associations occur in Chinese patients with IPCV from Singapore.

Methods:: Patients of Chinese ethnicity with clinically and angiographically diagnosed IPCV and age-matched normal controls were recruited into the study. Detailed characterization of the patient's phenotype was performed with fundal photography, fundus fluorescein and indocyanine green angiography. Genomic DNA was extracted from peripheral white blood cells. Exon 9 of the CFH gene and exon 7 of the C2 gene were amplified via polymerase chain reaction and subjected to bi-directional sequencing using BigDye Terminator v3.1 chemistries and analyzed on an ABI PRISM 3100 Genetic Analyzer for all patients. Normal controls DNA was subjected to restriction enzyme digest to determine the Y402H polymorphism in the CFH gene. Statistical analysis was performed with chi-squared test and Fisher's Exact test.

Results:: Fifty-three Chinese patients diagnosed with IPCV and 83 age-matched normal controls were recruited in the study. Seven (13.2%) patients with IPCV and eight (9.6%) normal controls were found to have the Y402H variant of CFH. Genotype frequency did not differ significantly between IPCV patients and controls [TT 86.8%, TC 13.2% and CC 0% in IPCV; TT 90.4%, TC 8.4% and CC 1.2% in controls, odds ratio (OR)=1.43, 95% confidence interval (CI) 0.49-4.2; p=0.52]. One (GC genotype, 1.9%) patient with IPCV and four (GC genotype, 4.8%) normal controls had the E318D variant of C2 (OR=0.61, 95% CI 0.04-3.5; p=0.65).

Conclusions:: Our preliminary results show that the Y402H variant in CFH is not associated with the risk of IPCV in Chinese subjects. The E318D variant of C2 though not statistically significant may confer a reduced risk of IPCV in our patients. This suggests a different genetic basis for IPCV compared to other forms of AMD.

Keywords: age-related macular degeneration • genetics • choroid: neovascularization