Higher order lipase gene association with plasma triglycerides

Area of Science:

• Biochemistry
• Genetics
• Cardiovascular Disease Research

Background:

• Lipoprotein lipase (LPL), HL, and endothelial lipase (EL) are key enzymes regulating plasma lipoprotein metabolism.
• These enzymes possess triglyceride (TG) lipase and phospholipase activities, influencing lipid levels.
• Individual single nucleotide polymorphisms (SNPs) in these genes are known to affect lipid profiles.

Purpose of the Study:

• To investigate the higher-order interactions between multiple SNPs in lipase genes and their combined impact on plasma lipoproteins.
• To determine if multilocus genotypes have a greater influence on plasma TG levels than individual SNPs.

Main Methods:

• A two-stage approach was used in a cohort of 738 asymptomatic Caucasian subjects.
• Subjects were grouped based on similar multilocus lipase genotypes.
• Permutation testing and mixed-effects modeling were employed to analyze genotype-lipid relationships.

Main Results:

• A significant higher-order interaction was identified between four specific SNPs in EL, HL, and LPL genes and plasma TG levels.
• Subjects heterozygous for all four SNPs exhibited significantly higher plasma TG levels compared to the additive effects of individual SNPs and environmental factors.
• These findings remained significant after correcting for multiple comparisons.

Conclusions:

• Lipase genes exhibit synergistic associations with plasma TG levels, extending beyond the effects of individual genes.
• Multilocus genotype contributions to dyslipidemia and atherosclerotic cardiovascular disease risk warrant consideration, as they can be significant even without strong individual gene effects.