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Thu. Apr 25th, 2024

Changes in genes that reduce Cholesterol may increase the incidence of Cataracts

The possibility of getting cataracts and requiring cataract surgery appears to be higher among those with genetic variants linked to decreasing LDL cholesterol similarly to Statin drugs, according to recent research published in the Journal of the American Heart Association (JAHA). 

There is some indication from earlier studies that Statins may make cataracts more likely.

Researchers investigated whether specific genes that mimic the effects of statins may potentially independently raise the likelihood of acquiring cataracts in this study. Statin drugs lower LDL cholesterol levels by blocking the HMG-CoA-reductase enzyme (HMGCR). Variants in the human genome’s HMGCR gene area have an impact on how people metabolise cholesterol, according to earlier studies.

It’s critical to emphasise that cataract surgery is both successful and safe, and that the benefits of statins for reducing low-density lipoprotein levels in persons with high blood cholesterol levels far outweigh any small risk of cataracts.

Researchers studied genetic information for more than 402,000 people using the UK Biobank, a sizable database of UK residents that follows major health and medical disorders in close to half a million adults. The study concentrated on five prevalent genetic variations that have been previously identified as lowering LDL cholesterol levels.

Based on the previously determined effects of each mutation on LDL cholesterol, they then generated genetic scores. To find people who carry an uncommon mutation called a predicted loss-of-function mutation in the HMGCR gene, genetic coding data was analysed.

“When we carry a loss-of-function mutation, the gene is less likely to work,” Ghouse said. “If that gene doesn’t work, the body can’t produce that protein. Simply put, the loss-of-function mutation in the HMGCR gene equals taking a statin medication.”

The study discovered that Individuals with a higher risk of cataracts and cataract surgery were identified by the HMGCR genetic risk score. The genetic score found that there was a 14 percent increased risk of cataracts and a 25 percent increased risk of cataract surgery for every 38.7 mg/dL reduction in LDL cholesterol.

32 (0.02 percent) of the 169,172 individuals having HMGCR sequencing data harboured one of the 17 unusual loss-of-function mutations predicted by the HMGCR. Carriers of these uncommon mutations were over 4.5 times more likely to acquire cataracts and over 5 times more likely to undergo cataract surgery than non-carriers.

Ghouse said he was surprised by the magnitude of the association. “The main difference between the two analyses is that loss-of-function mutations are really more detrimental than common variants, meaning they mimic change that is often induced by medications,” he said. “We believe that the true effect lies closer to the loss-of-function mutation association than the common variant association. When taking statins, you have an almost-complete inhibition of that protein, and when you have a loss-of-function mutation you also have a significantly reduced ability to produce that protein.”

The main drawback of the study, as stated by the author, is that while having these genetic variants increases a person’s risk of developing cataracts throughout their lifetime. This risk shouldn’t be assessed the same way for those who start taking statins later in life due to the potential benefits of lowering blood cholesterol levels. They further verified that whereas statin treatment often starts later in age, the relationships reflect lifelong treatment.

To support these findings, more clinical trials evaluating this connection are required.

The rationale is that by identifying and intensively monitoring a small group of individuals who have a childhood diagnosis of elevated cholesterol and begin statin therapy at a young age, be monitored for cataracts as well.

By Editor

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