A new study published today in the Journal of the American Heart Association shows that people with genetic variations that lower LDL cholesterol in a way similar to statins may be more likely to get cataracts and need surgery to fix them. 

There is some evidence that statin drugs may raise the risk of cataracts, according to a previous study. In this investigation, researchers looked into whether some genes that act similarly to statins could increase the risk of cataracts on their own.

Statins work by blocking an enzyme called HMG-CoA-reductase, which lowers LDL cholesterol levels (HMGCR). Previous research has shown that HMGCR gene variations alter cholesterol metabolism.

In this study, according to lead study author Jonas Ghouse, they “were able to establish a link between genetic variants that mimic HMGCR inhibition and the development of cataracts.” 

The lead author further adds: “We were not able to find any association between newer non-statin, lipid-lowering medications and cataract risk, so this effect is likely specific to statins.”

But “it’s important to stress that the benefits of statins for lowering levels of low-density lipoproteins in people who have high blood cholesterol levels completely outweighs the small risk of cataracts, and cataract surgery is effective and safe.”

Researchers studied genetic data for more than 402,000 people using the UK Biobank, a massive database of UK residents that follows significant health and medical disorders of almost half a million adults.

The researchers concentrated on five previously discovered genetic variations that reduce LDL cholesterol levels. They then generated genetic scores based on the influence of each mutation on LDL cholesterol that had previously been identified. The researchers looked through genetic coding data to see if anyone had a predicted loss-of-function mutation in the HMGCR gene.

“When we carry a loss-of-function mutation, the gene is less likely to work,” Ghouse adds. “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.”

According to the findings of the study:

• People with a higher risk of cataracts and cataract surgery were identified using the HMGCR genetic risk score. Cataract risk increased by 14 percent and the likelihood of cataract surgery increased by 25 percent with every decrease of 38.7 mg/dL in LDL cholesterol as determined by the genetic score.
• 32 (0.02 percent) of the 169,172 people who had HMGCR sequencing data had one of 17 rare HMGCR predicted loss-of-function mutations. More than four and a half times as likely to develop cataracts and more than five times as likely to have cataract surgery, people who carried these rare mutations were at a higher risk of developing cataracts than the general population.

Ghouse said that he was surprised by how big the link was.

“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.”

“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.”

One major limitation of the study, according to the authors, is that while carrying these genetic variants carries a lifelong risk of developing cataracts, that risk should not be evaluated the same way for people who start taking statins later in life, given the potential benefits of statins in lowering blood cholesterol levels. To corroborate these findings, further clinical trials examining this connection are needed.

“Our associations reflect lifelong treatment, whereas statin treatment typically occurs later in life,” Ghouse notes. “However, there is a specific group of patients who are diagnosed with high cholesterol in childhood and start statin treatment at a young age, so they could be identified and followed up more closely for cataracts.”

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