CFH polymorphisms in a Northern Spanish population with neovascular and dry forms of age-related macular degeneration

Abstract

Purpose: To elucidate the potential role of single-nucleotide polymorphisms (SNPs) in complement factor H (CFH) gene in Northern Spanish patients with age-related macular degeneration (AMD).

Methods: A case-control study of 130 unrelated native Northern Spanish diagnosed with AMD (46 dry, 35 neovascular and 49 mixed) and 96 healthy controls matched by age and ethnicity were enrolled. DNA was isolated from peripheral blood and genotyped for AMD-associated SNPs (rs3753394, rs529825, rs800292, rs3766404, rs203674, rs10671170, rs3753396 and rs1065489) using TaqMan probes and restriction fragment length polymorphism (RFLP). The association study was performed using the HaploView 4.0 software.

Results: The allelic frequency analysis revealed that rs529825, rs800292, rs203674 and rs10671170 were significantly associated with an increased risk for AMD. The haplotypes CGG (rs3753394, rs529825 and rs800292) and GCAG (rs203674, rs1061170, rs3753396 and rs1065489) were significantly associated with AMD while the haplotypes CAA (rs3753394, rs529825 and rs800292) and TTAG (rs203674, rs1061170, rs3753396 and rs1065489) were found to be protective. Small differ-ences in allelic frequencies were found between dry and neovascular cases; however, these differences were not significant and did not distinguish one form the other.

Conclusions: This study found significant association of SNPs rs529825, rs800292, rs203674 and rs1061170 in the CFH gene with susceptibility to AMD. We identified haplotypes that confer protection or increased risk of AMD but not specific genetic variants in CFH capable to distinguish the different clinical forms of AMD in this cohort. Collectively, our results confirmed that CFH represents a strong genetic risk factor for this disease in the Northern Spanish population.

Keywords: CFH gene; Neovascular; Northern Spanish population; age-related macular degeneration; dry AMD; genetic association; haplotypes; single-nucleotide polymorphism.