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Genetics

HMGCR and PCSK9 variants and cardiovascular risk

Nature Reviews Cardiology volume 14, page 66 (2017)Cite this article

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Genetic variation in PCSK9 that results in the lowering of LDL-cholesterol levels has a similar effect on the risk of cardiovascular events and diabetes mellitus to that of genetic variation in HMGCR (which encodes the protein target of statins). This finding comes from a study involving 112,772 participants from 14 studies, who were grouped according to the number of LDL-cholesterol-lowering alleles they had inherited. For each 10 mg/dl decrease in LDL-cholesterol level, the risk of cardiovascular events was reduced to a similar degree by variants in HMGCR (OR 0.81, 95% CI 0.72–0.90) or PCSK9 (OR 0.81, 95% CI 0.74–0.89). Individuals with these genetic variants and impaired fasting glucose levels were at increased risk of diabetes (OR 1.13, 95% CI 1.06–1.20 for HMGCR; OR 1.11, 95% CI 1.04–1.19 for PCSK9). Of note, “when present together, PCSK9 and HMGCR variants had additive effects on the risk of both cardiovascular events and diabetes”.

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References

  1. Ference, B. A. et al. Variation in PCSK9 and HMGCR and risk of cardiovascular disease and diabetes. N. Engl. J. Med. 375, 2144–2153 (2016)

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  1. Gregory B. Lim
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Lim, G. HMGCR and PCSK9 variants and cardiovascular risk. Nat Rev Cardiol 14, 66 (2017). https://doi.org/10.1038/nrcardio.2016.204

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