Abstract
Purpose: :
AMD is the most common cause of blindness in patients over age 50. Both hereditary and environmental factors appear to play a role in the disease’s pathogenesis. Modifiable risk factors include smoking, obesity and dietary antioxidants. Non-modifiable factors are gender (females show 2-fold greater risk), ethnicity (Caucasians show 2-fold greater risk than African Americans), age and genotype. The aim of this clinical study was to identify individuals with serologic markers of AMD.
Methods: :
Biological samples with matching demographic, clinical and medical history were collected from consenting healthy subjects and subjects with known medical conditions. Three hundred subjects, 18 to 77 years of age, with no known history or evidence of hepatitis C, hepatitis B or HIV were enrolled. Blood samples were obtained to identify donors that possess the risk or protective haplotype of complement factor H (CFH) associated with AMD (Hageman et. al., PNAS 2005). CFH and interferon gamma plasma concentrations were measured by qualified ELISAs. Recombinant human CFH protective protein made by Optherion was used as the CFH ELISA reference standard. Standard curves for other CFH reference standards were compared in this assay.
Results: :
Three categories of haplotypes were identified based solely on the alleles at Y402H and I62V (homozygous risk, homozygous protective, and "other"). Other is defined as haplotypes containing the alternate possibilities found at the Y402H and I62V positions. CFH plasma concentrations in subjects identified as homozygous for the risk (n=38) or protective (n=20) CFH haplotype were similar, with mean values ± 1 standard deviation of 250 ± 42 and 259 ± 57 µg/mL, respectively. CFH plasma concentrations were similar in subjects with the "other" haplotypes. There was also no influence of age and gender on CFH plasma concentrations, even when evaluated by genotype. The selection of CFH reference standard, ELISA format and assay antibodies influence the absolute value reported for CFH plasma concentration.
Conclusions: :
CFH plasma concentrations were comparable across CFH genotypes, all ages, and for males and females.Commercial Relationship: E: All authors are employees of Optherion, Inc.Support: All work was funded by Optherion, Inc.
Keywords: age-related macular degeneration