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Association of the HTRA1 -625G>A promoter gene polymorphism with exudative age-related macular degeneration in a Central European population.

PURPOSE: Exudative age-related macular degeneration (AMD) is one of the most common causes of severe visual loss. Both environmental and genetic factors, such as the complement factor H (CFH) 402H allele, have been associated with AMD. Recently, the HTRA1 -625A allele was identified as a novel risk marker in both a North American and a Chinese population. The present study was performed to evaluate the association of the HTRA1 -625A allele with exudative AMD in a Central European population.

METHODS: The present case-control study included 242 patients with exudative AMD and 157 control subjects. Genotypes of the HTRA1 -625G>A polymorphism were determined by a 5'-exonuclease assay (TaqMan). Determination of CFH Y402H genotypes was done by allele specific digestion of polymerase chain products.

RESULTS: Carriers of the HTRA1 -625AA genotype were found significantly more often in AMD patients than among control subjects (27.7% versus 5.1%; p<0.001). Binary logistic regression analysis binary logistic regression analysis revealed an odds ratio (OR) of 2.7 (95% confidence interval (CI): 1.1-6.8) for AMD among subjects heterozygous for the HTRA1 -625A allele compared to those with the wildtype genotype, when adjusted for CFH Y402H genotypes (p=0.034). The OR increased to 10.2 (95% CI: 3.0-34.5) among subjects homozygous for the HTRA1 -625A allele (p<0.001). The OR for AMD among heterozygous carriers of the CFH 402H variant was 3.6 (95% CI: 1.6-7.8) compared to those with the wildtype genotype, when adjusted for HTRA1 -625G>A genotypes (p=0.001). The OR increased to 9.8 (95% CI: 3.7-25.9) among subjects homozygous for the CFH 402HH genotype (p<0.001). Interaction terms between CFH and HTRA1 genotypes were not significantly associated with AMD.

CONCLUSIONS: Our data suggest that both the HTRA1 -625A allele and the CFH 402H allele are independently associated with exudative AMD in a Central European population.

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