Complement Factor Y402H polymorphism is not associated with Stargardt’s Disease in Italian Patients

Abstract

Purpose: As CFH Y402H polymorphisms has been associated with a higher risk of AMD, clinical, physiopathological and genetic affinities between atrophic AMD and STGD may suggest a possible role of CFH abnormalities also in STGD. The possible association of Y402H and STGD has been investigated in Italian patients.

Methods: One-hundred unrelated STGD patients and 116 patients with advanced atrophic AMD were recruited through the Hereditary Retinal Degenerations Referring Center and the Medical Retina Service of the Eye Clinic, University of Florence . The control group consisted of 100 healthy volunteers. Each patient was genotyped for the single nucleotide polymorphism rs1061170 (Y402H) in the CFH gene using Sequencer 3730 DNA Analyzer. Hardy Weinberg equilibrium was tested using the two sided Pearson's chi-squared test with Yates' continuity correction. Genotype frequency distributions between cases and controls were compared by means of chi squared test for heterogeneity. Univariate unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for the association between genotypes and diseases under investigation. In addition, the multiplicative and additive genetic models were used for the analysis. All statistical analyses were performed using SAS System 9.2.

Results: Among all the three groups of controls, patients with AMD and patients with STGD, the genotype distribution of Y402H1 was in Hardy Weinberg equilibrium (P=0.327, P=0.320 and P=0.450, respectively). The genotype frequency of Y402H1 were different between patients with AMD and controls (P=0.0003). In the additive model CT genotype was associated with approximately 2.5 times higher odds of disease compared with TT genotype, while CC genotype demonstrated a risk of disease about 5 times higher than the reference group (P for trend<0.0001). Similar genotype frequencies of Y402H1 were observed between patients with STGD and controls (P=0.4882). In this case, the estimates of risk were compatible with the multiplicative genetic model, however results did not achieve the statistical significance (P=0.2639).

Conclusions: In Italian patients CFH Y402H genotype is associated with atrrophic AMD but not with Stargardt’s Disease. This result does not support the hypothesis of a complement system dysregulation in the pathogenesis of Stargardt’s Disease.

Keywords: 688 retina • 539 genetics • 696 retinal degenerations: hereditary