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.
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 CFHY402H genotypes was done by allele specific digestion of polymerase chain products. RESULTS: Carriers of the HTRA1 -625AA genotype were found significantly more often in AMDpatients 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 CFHY402H 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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Authors: Reecha Sofat; Juan P Casas; Andrew R Webster; Alan C Bird; Samantha S Mann; John R W Yates; Anthony T Moore; Tiina Sepp; Valentina Cipriani; Catey Bunce; Jane C Khan; Humma Shahid; Anand Swaroop; Gonçalo Abecasis; Kari E H Branham; Sepideh Zareparsi; Arthur A Bergen; Caroline C W Klaver; Dominique C Baas; Kang Zhang; Yuhong Chen; Daniel Gibbs; Bernhard H F Weber; Claudia N Keilhauer; Lars G Fritsche; Andrew Lotery; Angela J Cree; Helen L Griffiths; Shomi S Bhattacharya; Li L Chen; Sharon A Jenkins; Tunde Peto; Mark Lathrop; Thierry Leveillard; Michael B Gorin; Daniel E Weeks; Maria Carolina Ortube; Robert E Ferrell; Johanna Jakobsdottir; Yvette P Conley; Mati Rahu; Johan H Seland; Gisele Soubrane; Fotis Topouzis; Jesus Vioque; Laura Tomazzoli; Ian Young; John Whittaker; Usha Chakravarthy; Paulus T V M de Jong; Liam Smeeth; Astrid Fletcher; Aroon D Hingorani Journal: Int J Epidemiol Date: 2012-01-13 Impact factor: 7.196
Authors: Anna-Maija Tolppanen; Tanja Nevalainen; Marjukka Kolehmainen; Sanna Seitsonen; Ilkka Immonen; Matti Uusitupa; Kai Kaarniranta; Leena Pulkkinen Journal: Mol Vis Date: 2009-04-15 Impact factor: 2.367