Purpose: Two common single nucleotide polymorphisms (SNPs) in the CX3CR1 gene, T280M and V249I, have been reported to affect the risk of age-related macular degeneration (AMD) in several studies. The aim of the present study was to combine all published data on the relationship between these two variants and AMD susceptibility in a meta-analysis to clarify this association.

Methods: MEDLINE, EMBASE, and ISI Web of Science were searched for all eligible studies on the relationship between AMD and T280M and V249I variants. The pooled odds ratio (OR) with 95% confidence intervals (CIs) for each SNP in the allele frequency, homozygote, second codominant genotype, and dominant genotype models were calculated to evaluate the strength of this association.

Results: A total of 3017 AMD cases and 4096 controls from eight studies were involved in this meta-analysis. Both T280M and V249I SNPs exhibited significant associations with increased risk of AMD in the allele (T versus C: OR= 1.43, 95% CI: 1.06–1.91; A versus G: OR= 1.25, 95% CI: 1.01–1.55) and homozygous models (TT versus CC: OR= 2.11, 95% CI: 1.00–4.43; AA versus GG: OR= 1.27, 95% CI: 1.00–1.61), while no significance association was observed for the codominant genotype model. Moreover, studies showing high linkage disequilibrium between these two variants demonstrated a significantly stronger connection between these SNPs and AMD risk, compared with the moderate linkage disequilibrium group.

Conclusions: Significant evidence for a relationship between T280M and V249I variants in CX3CR1 in the homozygote state with increased susceptibility to AMD was reported. Further studies are needed to confirm these findings.