Mar 14, 2019

Mendelian Randomization Study of ACLY and Cardiovascular Disease

The New England Journal of Medicine
Brian A FerenceStephen J Nicholls

Abstract

ATP citrate lyase is an enzyme in the cholesterol-biosynthesis pathway upstream of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the target of statins. Whether the genetic inhibition of ATP citrate lyase is associated with deleterious outcomes and whether it has the same effect, per unit decrease in the low-density lipoprotein (LDL) cholesterol level, as the genetic inhibition of HMGCR is unclear. We constructed genetic scores composed of independently inherited variants in the genes encoding ATP citrate lyase (ACLY) and HMGCR to create instruments that mimic the effect of ATP citrate lyase inhibitors and HMGCR inhibitors (statins), respectively. We then compared the associations of these genetic scores with plasma lipid levels, lipoprotein levels, and the risk of cardiovascular events and cancer. A total of 654,783 participants, including 105,429 participants who had major cardiovascular events, were included in the study. The ACLY and HMGCR scores were associated with similar patterns of changes in plasma lipid and lipoprotein levels and with similar effects on the risk of cardiovascular events per decrease of 10 mg per deciliter in the LDL cholesterol level: odds ratio for cardiovascular events, 0.823 (95% confide...Continue Reading

  • References24
  • Citations36

Citations

Mentioned in this Paper

EEF1A2
Study
Mendelian Randomization Analysis
ACLY
Genes
Cholesterol Biosynthetic Process
HMGCR gene
Inhibitors
Hydroxymethylglutaryl-CoA reductase
Hypercholesterolemia

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