98th Annual Meeting DOG 2000

V 20

Prevalence of CST3 genotypes in patients with exudative ARMD and control subjects

J. Zurdel, U. Finck, G. Richard, R. M. Nitsch

Background: We intended to determine the prevalence of CST3 genotypes among patients with exudative ARMD and control subjects.

Methods: 167 patients with exudative ARMD, consisting of all subtypes were recruited and the diagnosis of neovascular ARMD was documented by fluorescein angiography. CST3 genotypes of these patients were analyzed using PCR and restriction enzyme digestion with SacII and were compared to those of 268 age-matched and ethnically-matched control subjects as well as to those of 440 control subjects who were not age-matched. All control subjects were randomly selected and can be expected to develop the disease at the population rate.

Results: Genotype counts of CST3 haplotypes did not significantly deviate from those expected under Hardy-Weinberg equilibrium. The frequency of the CST3 genotype BB was significantly higher in patients with exudative ARMD than in age-matched controls (0.066 vs 0.024; p=0.023). The frequency imbalance was statistically significant for the male gender (0.113 vs. 0.024; p=0.012), whereas no statistically significant difference was found for the female subgroup (0.044 vs.0.021; p=0.30). Results were similar when the frequency of CST3 BB genotype in patients was compared to controls who were not age-matched (0.066 vs. 0.025; p=0.016). Again, the frequency imbalance was statistically significant in men (0.113 vs. 0.018; p=0.001) but not in women (p=0.57). Kaplan-Meier survival analysis revealed a mean disease-free survival time of 83 years for the pooled CST3 AA and AB subjects (95% CI=80-85; S.E.=1) versus 75 years for CST3 BB subjects (95% CI=71-79; S.E.=2) (Mantel-Cox Log rank=9.00; df=1; p=0.0027).

Discussion: There is a genetic association of the CST3 genotype BB with exudative ARMD establishing a role of CST3 BB as a genetic risk factor for exudative ARMD. Our data suggest that the association of CST3 BB and exudative ARMD is dependent on gender.

University Eye Hospital, Martinistr.52, D-20246 Hamburg