Association of Two Polymorphisms, rs1061170 and rs1410996, in Complement Factor H with Age-Related Macular Degeneration in an Asian Population: A Meta-Analysis

Abstract

Background: With the increasing number of studies indicating that two single-nucleotide polymorphisms (SNPs), rs1061170 and rs1410996, in complement factor H (CFH) might be associated with the susceptibility to age-related macular degeneration (AMD), the exact association still remains uncertain. Thus, we conducted a meta-analysis to systematically summarize and clarify the association between the two SNPs and the AMD risk particularly in an Asian population. Methods: A systematic search of studies on the association of two SNPs with the susceptibility to AMD was conducted in PubMed, Embase and Web of Science. Summary odds ratios (ORs) and 95% confidence intervals (CIs) of allele contrast and genotype contrast were estimated using the random or fixed effects model. The Q statistic test was used to identify heterogeneity, and the funnel plot was adopted to evaluate publication bias. A total of 19 case-control studies on rs1061170 and 8 studies on rs1410996 were included. Results: Clearly a significantly increased trend of AMD was observed with the rs1061170 (T vs. C: OR = 1.91, 95% CI = 1.71-2.13, p_H = 0.029; TC vs. CC: OR = 2.11, 95% CI = 1.30-3.42, p_H = 0.792; TT vs. CC: OR = 3.90, 95% CI = 2.45-6.22, p_H = 0.774). Similarly, the rs1410996 polymorphism also showed a rising AMD tendency (T vs. C: OR = 1.48, 95% CI = 1.17-1.87, p_H < 0.001; TC vs. CC: OR = 1.52, 95% CI = 1.13-2.04, p_H = 0.002; TT vs. CC: OR = 2.10, 95% CI = 1.27-3.49, p_H < 0.001). What is more, subgroup analysis revealed that both polymorphisms indicated a high risk of nAMD (neovascular AMD) in Asian populations. Conclusions: This meta-analysis suggested that CFH rs1061170 and rs1410996 polymorphisms were associated with AMD risk, both of which demonstrated a higher susceptibility to AMD, especially to nAMD. However, the results of rs1410996 should be interpreted with caution due to the limited sample and heterogeneity. Large-scale and well-designed studies are needed to validate our findings.

The association between complement factor H rs1061170 polymorphism and age‐related macular degeneration: a comprehensive meta‐analysis stratified by stage of disease and ethnicity

“…; Wu et al. ), our results showed a significant association between the rs1061170 polymorphism and the risk of all AMD subtypes, with a summary allele OR of 2.15. However, our analysis indicated significant between‐study heterogeneity, with an I 2 measure that ranged from 81.2% to 92.4% in any genetic model.…”

“…It has been observed that the strength of the association between rs1061170 polymorphism and AMD seems to be lower when studies move from the West to the East, and the compelling association, observed in European cohorts, was not as relevant to the AMD risk in populations of Asian ancestry (Wu et al. ). Individual studies have been performed in Asian populations, but most of these reported a lack of association in Korean, Japanese and Chinese (Chen et al.…”

“…suggested that the effect might be more relevant for the CNV, thought the related mechanism still remained uncertain (Wu et al. ).…”

Early and intermediate age-related macular degeneration: update and clinical review

“…In addition to age-related changes, it has been shown that genetic factors significantly contribute to risk for advanced AMD 10,11. About 20 genes involved in the pathogenesis of AMD have been identified, the most important being CFH , C3 , C2 , ARMS2 , FB , CFHR4 , CFHR5 , and F13B .…”

Association between Drusen Burden Determined by OCT and Genetic Risk in Early and Intermediate Age-Related Macular Degeneration

“…23 A combination of drusen parameters along with other OCT derived parameters such as hyperreflective foci and retinal thickness may be the most informative and predictive of progression. 15,16,23 The association between advanced AMD and the CFH Y402H variant as well as the intronic SNP in this gene, CFH rs1410996, have been well documented 6,20,34,38,[49][50][51] The biologic mechanisms underlying their effect on drusen accumulation, however, have not been fully explored. In our previous analyses of these variants regarding progression, the effect of rs1410996 was stronger and the effect of Y402H was reduced when both were in the same model, suggesting that this variant may be more strongly associated with AMD.…”