Association of the complement factor H Y402H polymorphism and response to anti-VEGF treatment in age-related macular degeneration: An updated meta-analysis
Amirhossein Roshanshad1 *, Seyed Ali Moosavi1
- Poostchi Ophthalmology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Abstract: Different response of age-related macular degeneration (AMD) to anti-vascular endothelial growth factor (anti-VEGF) agents has been attributed to several items including genetic factors. We systematically reviewed the effects of SNP rs1061170/Y402H of the CFH gene and its possible confounders on AMD response to anti-VEGF therapy with a larger number of Asian participants.
Methods: We comprehensively searched MEDLINE (PubMed), Scopus, EMBASE, Web of Science, and Google Scholar. Pooled odds ratios (ORs) and its 95% CIs were estimated using Stata V.14.0. Statistical heterogeneity was measured using I2 statistics.
Results: Twenty-five papers were included in meta-analysis including a total of 4835 eyes of 4681 patients. For overall population, better response to anti-VEGF therapy was seen in T over C (OR = 1.25, 95% CI = 1.04–1.50), TT over CC (OR = 1.60, 95% CI = 1.06–2.4), and TT+TC over CC (OR = 1.68, 95% CI = 1.23–2.28) genotypes. In other three genetic models (TT vs. TC, TT vs. TC+CC, and TC vs. TT+CC), no significant difference was observed between genotypes. In Asians, no significant difference in response to treatment was observed in all six genetic models; however, TT and CC genotypes showed better response to treatment compared to TC genotype [TT vs. TC(OR = 1.31, 95% CI = 0.93–1.82)] [TC vs. TT+CC(OR = 0.77, 95% CI = 0.55–1.07)]. Our study also revealed similar efficacy of ranibizumab and bevacizumab; however, Conbercept was more effective in homozygous genotypes. Subgroup analysis based on the definition of response to anti-VEGF treatment indicated that TT and TC genotypes and T allele were associated with better functional response, while CC genotype and C allele were accompanied by better anatomical response. Finally, combination of risk alleles of ARMS2 A69S (rs10490924), VEGF-A (rs699947), and VEGF-A (rs833069) with Y420H is a predictor of non-respondents to anti-VEGF therapy.
Conclusion: CFH Y402H gene may be a predictor of response to anti-VEGF agents in AMD. Conbercept might be more effective in homozygous genotypes. Besides, while TT and TC genotypes showed better functional response, CC genotype was accompanied with better anatomical response.
