Genetics and Statins in the Progression for Age-Related Macular Degeneration
DOI:
https://doi.org/10.48560/rspo.33192Keywords:
Disease Progression, Genetic Predisposition to Disease, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Macular Degeneration/geneticsAbstract
INTRODUCTION: Age-related macular degeneration (AMD) is a multifactorial disease with unclear pathophysiology. One of the pathways identified is lipid metabolism. Drusen, AMD hallmark, are lipid-rich deposits. Additionally, genes participating in lipid homeostasis are associated with the disease. Statins have been studied as possible protective drugs against AMD, though inconclusively. We aim to explore statin’s role in AMD progression, considering AMD genetic risk, in the Coimbra Eye Study.MATERIAL AND METHODS: Six hundred eighty-three subjects (1321 eyes): 112 subjects (168 eyes) progressed over 6.5 years, and 561 subjects (1153 eyes) did not. Progressors were subjects who progressed from grade 0, 1a or 1b to grades 2,3 or 4 between visits (Rotterdam Classification). Only subjects taking statins between visits were considered. A Genetic Risk Score was calculated using 52 SNPs. Strength of statins was defined as high, medium, and low, according to INFARMED guidelines. To investigate the association between statins and AMD progression, an extended Cox regression analysis was used, adjusted for baseline-age, -sex, -body mass index, -smoking, -diabetes, and -arterial hypertension. Statin use was corrected by the genetic risk score. Correlation between eyes was considered.
RESULTS: The use of statins was significantly associated with a decreased risk in AMD progression (HR=0.509, 95% CI 0.302-0.860, p=0.012), when corrected for age, sex, body mass index, smoking, diabetes and arterial hypertension. This association was maintained for medium- and high-dose statins (HR=0.482, 95% CI 0.285-0.814, p= 0.006), but not for low-dose statins (HR=1.321, 95% CI 0.159-10.995, p= 0.797), corrected for the same variables. After controlling for the Genetic Risk Score, statins remained significantly associated with a risk reduction for AMD progression (HR=0.516, 95% CI 0.293-0.91, p= 0.022).
CONCLUSION: The use of statins suggested a protection against AMD progression after controlling for age, sex, obesity, smoking habits, diabetes and arterial hypertension, highlighting lipids involvement in AMD pathophysiology. When considering AMD genetic risk, statins maintained its association with a decreased risk of progression. Our results indicate a benefit of these drugs in the delay of the disease course, even weighting the AMD genetic profile, contributing to a possible therapeutic strategy.
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