Macula Risk^® tests for several Single Nucleotide Polymorphisms (SNPs) and Haplotypes that strongly affect the genetic risk of AMD. The inheritance of AMD risk associated with each gene is independent of the risk associated with any other AMD gene. Several of these gene variants promote inflammation, by altering activation of the complement cascade, an aspect of innate immunity. Other gene variants affect mitochondrial function and increase oxidative stress in the retina, consistent with both the role of smoking as a risk factor and the benefit of antioxidants in delaying disease progression. All of the genetic markers included in the Macula Risk test have validated in at least 2 independent studies

Complement Pathway

The first genetic association of a complement mutation with AMD was in 2005, a mutation in Complement Factor H which identified a change in a tyrosine (Y) codon at position 402 to histidine (H), producing a Y402H polymorphism. A short time later work from the University of Michigan identified that the Y402H polymorphism was but one marker and that a series of polymorphisms in the CFH gene, represented as haplotypes were more effective predictors of AMD.

An additional component of the complement pathway, C3 adds to the predictive value of Macula Risk.  The NEJM reported in 2007 “Complement C3 is important in the pathogenesis of age-related macular degeneration. This finding further underscores the influence of the complement pathway in the pathogenesis of this disease.”