Association of the HTRA1 -625G>A promoter gene polymorphismwith exudative age-related macular degeneration in a Central Europeanpopulation

[摘要] Purpose: Exudative age-related macular degeneration (AMD) is one ofthe most common causes of severe visual loss. Both environmental andgenetic factors, such as the complement factor H (CFH) 402H allele, havebeen associated with AMD. Recently, the HTRA1 -625A allele wasidentified as a novel risk marker in both a North American and a Chinesepopulation. The present study was performed to evaluate the associationof the HTRA1 -625A allele with exudative AMD in a Central Europeanpopulation.Methods: The present case-control study included 242 patients withexudative 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 specificdigestion of polymerase chain products.Results: Carriers of the HTRA1 -625AA genotype were foundsignificantly more often in AMD patients than among control subjects(27.7% versus 5.1%; p<0.001). Binary logistic regression analysisbinary logistic regression analysis revealed an odds ratio (OR) of 2.7(95% confidence interval (CI): 1.1-6.8) for AMD among subjectsheterozygous for the HTRA1 -625A allele compared to those with thewildtype genotype, when adjusted for CFH Y402H genotypes (p=0.034). TheOR increased to 10.2 (95% CI: 3.0-34.5) among subjects homozygous forthe HTRA1 -625A allele (p<0.001). The OR for AMD among heterozygouscarriers of the CFH 402H variant was 3.6 (95% CI: 1.6-7.8) compared tothose with the wildtype genotype, when adjusted for HTRA1 -625G>Agenotypes (p=0.001). The OR increased to 9.8 (95% CI: 3.7-25.9) amongsubjects homozygous for the CFH 402HH genotype (p<0.001). Interactionterms between CFH and HTRA1 genotypes were not significantly associatedwith AMD.Conclusions: Our data suggest that both the HTRA1 -625A allele andthe CFH 402H allele are independently associated with exudative AMD in aCentral European population.

[学科分类] 生物化学/生物物理