Complement Factor I Polymorphism Is Not Associated with Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in a Chinese Population

Abstract

Purpose: To identify the associations of the two complement factor I (CFI) polymorphisms rs10033900 and rs2285714 with risk of neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in a Chinese case-control study. Methods: A total of 900 subjects - 300 controls, 300 cases with nAMD and 300 cases with PCV - were included in the present study. Genomic DNA was extracted from venous blood leukocytes. The allelic variants of rs10033900 and rs2285714 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The differences in allele distribution between the cases and controls were tested by a χ² test with age and gender adjusted for by logistic regression analysis. We also performed a meta-analysis of the case-control studies of rs10033900 and rs2285714 based on the currently available evidence from the literature. The meta-analysis was conducted via an inverse-variance, fixed-effects model, as previously described. Results: No statistically significant association was observed between the two polymorphisms of CFI and AMD risk, including nAMD, PCV and combined AMD (p > 0.05 for all comparisons). By meta-analysis, we detected significant associations between both of the SNPs and late AMD, which is consistent with previous results (odds ratio, OR, rs10033900 = 0.814, p rs10033900 < 0.001; OR rs2285714 = 1.221, p rs2285714 < 0.001). For rs2285714, the results of the meta-analysis were less reliable due to its heterogeneity. Conclusions: In our case-control study, neither of the two SNPs most studied (rs10033900 or rs2285714) in the CFI gene was a risk factor for developing nAMD or PCV in a Chinese population. Additional large, comprehensive and well-designed association studies are needed to better understand the role of ethnicity and other gene interactions in the association between the CFI gene and AMD.

Complement Factor I Gene Polymorphism in a Turkish Age-Related Macular Degeneration Population

“…Cipriani et al [15] were not able to obtain significant results for the rs10033900 polymorphism in British and Scottish patient groups (p = 0.50 and p = 0.76, respectively). In addition, Yang et al [16] reported in a study including 600 patients with wet-type AMD and polypoidal choroidal vasculopathy and 300 controls in a Chinese population, no significant relationship between the polymorphism and the disease (rs10033900 p = 0.823, rs2285714 p = 0.437). Hence, in different population groups, each disease type and polymorphism may differ with respect to its features.…”

“…Further, Fagerness et al [4] demonstrated the relationship between AMD and rs10033900, which is a common single nucleotide polymorphism (SNP) of CFI. The SNP of CFI have been studied in different countries and populations, with various results describing its association with AMD [12][13][14][15][16].…”

Complement family member CFI polymorphisms and AMD susceptibility from a comprehensive analysis

“…Another molecular CFI remains equivocal. Yang et al made a meta-analysis that rs10033900 and rs2285714 SNPs had significant associations with AMD risk [32], whose report was indelicate that subgroups was not analyzed. An additional article in 2019 has been published, so we performed an updated meta-analysis to come to a more convincing conclusion about CFI gene polymorphisms and AMD susceptibility.…”

“…The full texts were then evaluated, and 198 additional articles were excluded due to duplication (154), meta-analysis or systematic analysis (28), only case group (4), and no data for each genotype (12). Finally, 11 different articles [23][24][25][26][27][28][29][30][31][32][33] were included in our meta-analysis, including 12 case-control studies about CFI gene rs10033900 polymorphism and total AMD risk and 3 case-control studies about rs2285714 polymorphism and AMD risk. The available clinical information in all publications were shown in Supplementary Table S1.…”

Latest Development on Genetics of Common Retinal Diseases

“…However, in a Chinese cohort, the SKI2 subunit of superkiller complex ( SKIC2 , also known as SKIV2L ) gene, rather than C2 or CFB , was the gene variant associated with nAMD in the C2-CFB-negative elongation factor complex member E ( NELFE , also known as RDBP ) -SKIV2L locus 38. Also, C3 39 and CFI 40 were not associated with nAMD in other Chinese cohorts, suggesting ethnic diversities.…”