Hepatic lipase, genetically elevated high-density lipoprotein, and risk of ischemic cardiovascular disease

Area of Science:

• Cardiovascular Genetics
• Lipid Metabolism
• Pharmacogenomics

Background:

• Hepatic lipase plays a crucial role in high-density lipoprotein (HDL) metabolism.
• HDL is a significant risk factor for ischemic cardiovascular disease (ICD), encompassing ischemic heart disease and ischemic cerebrovascular disease.

Purpose of the Study:

• To investigate the hypothesis that specific genetic variations in the hepatic lipase gene influence lipid and lipoprotein levels.
• To determine the association between these hepatic lipase genetic variants and the risk of developing ICD.

Main Methods:

• A large-scale cross-sectional and prospective study involving 9003 individuals from the Copenhagen City Heart Study.
• Genotyping was performed for several hepatic lipase variants (V73M, N193S, S267F, L334F, T383M, and -480c>t).
• Follow-up included incident ICD events over 28 years, with case-control analyses for ischemic heart disease and cerebrovascular disease.

Main Results:

• Hepatic lipase variants S267F and -480c>t were associated with statistically significant increases in HDL cholesterol levels.
• Theoretical calculations suggested these HDL increases should correlate with reduced ICD risk.
• However, observed odds ratios for ICD in carriers of these variants did not consistently differ from non-carriers, indicating no significant association with ICD risk.

Conclusions:

• Specific hepatic lipase genetic variants that elevate HDL cholesterol levels were not found to be associated with an increased risk of ischemic cardiovascular disease.
• The study highlights a dissociation between genetically influenced HDL levels and actual ICD risk, suggesting complex regulatory mechanisms.
• Further investigation is warranted to fully elucidate the role of hepatic lipase genetic variations in cardiovascular disease pathogenesis.