Statins and hemorrhagic stroke: New insight from a Mendelian randomization study

Area of Science:

• Genetics
• Pharmacology
• Neurology

Background:

• The association between statin use and hemorrhagic stroke (HS) risk is controversial.
• Causality between statin usage and HS risk remains unclarified in existing clinical studies.

Purpose of the Study:

• To investigate the causal effects of statin on HS risk using the Summary-data-based Mendelian randomization (SMR) method.
• To explore differences in the pattern of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) gene expression affecting HS between blood and brain tissues.

Main Methods:

• Employed the Summary-data-based Mendelian randomization (SMR) method.
• Utilized single-nucleotide polymorphisms (SNPs) associated with HMGCR gene expression to proxy statin's pleiotropic effects.
• Conducted comparative analysis between blood and brain HMGCR expression patterns related to HS risk.

Main Results:

• Higher blood HMGCR expression was associated with a decreased risk of subarachnoid hemorrhage (SAH) (OR=0.64).
• Brain HMGCR gene expression showed a borderline significant association with increased SAH risk (OR=1.11).
• A negative correlation was observed between blood and brain HMGCR expression patterns concerning HS and gene expression.

Conclusions:

• HMGCR expression in the brain is suggested to increase HS risk.
• Discrepancies in previous studies may stem from differing HMGCR gene expression patterns in the brain versus blood.
• Lipophilic statins may offer greater protection against HS risk compared to hydrophilic statins.