Danish researchers have found that a genetic proxy that mimics statin treatment is associated with an increased risk of cataract development and the need for cataract surgery.1
The findings lend support to previous studies linking statins to lens opacities. But while none of those earlier studies conclusively demonstrated an association between statins and the risk of cataract development, this study is different, said Jonas Ghouse, MD, PhD, at Copenhagen University Hospital in Denmark. “Using genetics, we were able to show that proxies for lifelong statin treatment may increase the risk of lenticular opacities.”
Study design. The researchers considered whether the presence of deleterious mutations in the HMGCR gene, which encodes HMG-CoA reductase, are associated with the risk of cataract and/or cataract surgery. (HMG-CoA reductase is a crucial enzyme in the cholesterol pathway and thus is the target of statins.)
To test their hypothesis, they analyzed UK Biobank genetic sequencing data of more than 402,000 unrelated European individuals between 40 and 69 years of age. The Biobank data allowed them to create a genetic score weighted by each variant’s ability to lower low-density lipoprotein (LDL) cholesterol. Variants with larger effects were given larger weights.
ASSOCIATION. Both common and rare variants of the HMGCR gene were linked to cataract development.
Link emerges. The researchers found a strong association between the HMGCR score and LDL levels. Specifically, a 38.7 mg/dL reduction in LDL score was associated with higher risk for both cataract (odds ratio [OR], 1.14) and cataract surgery (OR, 1.25).
To investigate whether the reported association was specific to the HMG-CoA pathway, the researchers looked at cataract risk associations between other genetic variants with known cholesterol-lowering effects. In particular, they considered genetically proxied inhibition of PCSK9 and NPC1L1 on circulating LDL levels and cataract. They found no association.
“What was important to investigate was whether it was the inhibition of the gene, rather than a global lowering of the cholesterol, that caused the reported association,” Dr. Ghouse said. “These results indicated that it was the inhibition of HMGCR, and not general LDL-lowering, that was associated with cataract risk.”
Clinical implications. Dr. Ghouse stressed that the reported gene association mimics long-term statin treatment, as occurs in patients with familial hypercholesterolemia. Thus, they may not translate to the initiation of statins later in life. For now, the findings should not deter treatment, but they should be disclosed to patients, he recommended.
1 Ghouse J et al. J Am Heart Assoc. 2022;11(12):3025361.
Relevant financial disclosures: Dr. Ghouse—None.
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