Pharmacogenomics and Age-Related Macular Degeneration

Controversy over the links between supplementation, genomics, and treatment response may have been due to researchers asking the wrong question.

By Demetrios G. Vavvas, MD, PhD

Pharmacogenomics is the study of the interaction between drugs and the human genome, in an effort to use a rational approach to maximize individual patient benefits and minimize adverse events. This potential was recognized as early as 510 BC by Pythagoras of Samos, when he noticed a connection between fava bean ingestion and hemolytic anemia in certain people.1,2 It was not until 1961 that a deficiency in G6PD was found to be responsible for favism. Around the same time, it was recognized that abnormalities in butyrylcholinesterase can result in serious adverse reactions after succinylcholine-aided anesthesia. It took another half century before we had the first FDA-approved pharmacogenetic test for cytochrome CYP2D6 and CYP2C19 alleles. The FDA requires many drugs to carry labels warning of specific gene interactions (


• Pharmacogenomics is the study of the interaction between drugs and the genome.
• More than 30 genes affect the risk for and progression of AMD.
• Used in clinical practice and in the management of patients with wet AMD, genetic information can help us better understand and treat the disease.


Age-related macular degeneration (AMD) is one of the most genetically influenced multigenic diseases found in humans, with more than 30 genes known to affect its risk and progression.3,4 Variants of two particular genes, complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2), have the strongest influence on AMD development and progression. These genes have been shown not only to affect progression to the diseased state but also to affect patients’ responses to therapy.

A meta-analysis by Chen and colleagues of 13 studies involving more than 2,700 patients concluded that CFH Y402H polymorphism may play a role in patients’ response to anti-VEGF treatment for wet AMD, especially for white individuals.5 Similar results were found in the most recent and comprehensive meta-analysis, including more than 2,960 patients. Those authors reported that “individuals carrying the rs1061170/Y402H TT genotype were more likely to achieve a better treatment outcome (OR = 1.932, 95% CI = 1.125–3.317, P = .017) than those carrying the CC genotype.”6

Another meta-analysis examining the ARMS2 A69S rs10490924 risk allele in more than 2,380 patients found that patients homozygous for the low-risk allele (GG) had a higher chance of better response compared with patients with TG or TT alleles (OR 1.34; P = 0.039). However, the subgroup analysis suggested that this finding may be driven by the Asian population and may not hold true in whites.7……….

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Source: Retina Today