Lipid-lowering drugs for AMD? Genotyping may guide treatment

Lipid-lowering drugs appear to exert a beneficial effect on age-related macular degeneration (AMD) but only in the presence of the rs1061170 genetic variant located in the CFH gene, as shown in a Singapore study.

In the Singapore Epidemiology of Eye Diseases (SEED), lipid-lowering drugs were associated with reduced odds of AMD progression among individuals carrying at least one C allele (inverse treatment probability weights [ITPW] method: odds ratio [OR], 0.41, 95 percent confidence interval [CI], 0.19–0.87; p=0.020; overlap weight [OW] method: OR, 0.45, 95 percent CI, 0.22–0.96, p=0.039). [iScience 2024;27:111344]

The finding was replicated in the UK Biobank, with lipid-lowering drugs showing a protective effect on AMD incidence among individuals with the CC genotype (ITPW method: hazard ratio [HR], 0.65, 95 percent CI, 0.45–0.93; p=0.019; OW method: HR, 0.67, 95 percent CI, 0.47–0.96; p=0.027).

In SEED, a subgroup analysis limited to statin specifically yielded similar results for individuals with at least one C allele of rs1061170 in the CFH gene (ITPW method: OR, 0.46, 95 percent CI, 0.21–1.01; p=0.052; OW method: OR, 0.52, 95 percent CI, 0.24–1.11; p=0.091).

“This indicates a possible avenue for the development of a targeted, personalized therapy based on the complement genotyping for patients with early form of the disease and thus at risk of progressing,” the investigators said.

“An approach could be to genotype for CFH genetic variant of interest in patients with early AMD and appropriate lipid-lowering drug commenced if a risk allele is detected. These drugs are well known, safe, and are widely used for common systemic conditions and would require only a change in indication if proven to prevent AMD progression,” they added.

Lipid metabolism in the retina

According to the investigators, the benefit of lipid-lowering drugs seen in individuals with the C allele of rs1061170 in the CFH gene may be due to the complex relationship between the complement system and lipid metabolism in the retina.

“In our analyses, we showed that lipid-lowering drug [use] was associated with an overall decrease in the level of the triglyceride sub-fraction in very large high-density lipoprotein (HDL) particles,” they said. “Therefore, the protective effect of [such drugs] for AMD progression may be due to decreased inflammation levels associated with a lower concentration of triglycerides sub-fraction in very large HDL particles.”

The investigators called for biological studies to determine the functional effect of rs1061170 genetic variant polymorphism.

The study included 5,579 individuals in SEED and 445,727 in UK Biobank.

In SEED, 1,251 individuals used lipid-lowering drugs (median age 61.1 years, 49.7 percent female, 39.2 percent Chinese) at baseline. AMD occurred in 484 individuals (18.7 percent), of which 216 showed progression over 6 years of follow-up. Compared with those who remained free of AMD, individuals with AMD tended to be older, male, Chinese or Malay, to have hypertension, to be past smokers, and to have no primary education level.

In UK Biobank, 77,864 individuals (17.3 percent) used lipid-lowering drugs at baseline. Over a mean follow-up of 6.9 years, AMD occurred in 913 individuals. Those with AMD were more likely to be older, to have diabetes and cardiovascular disease, and to be past smokers relative to individuals who remained free of AMD during the follow-up.