Title : Higher order lipase gene association with plasma triglycerides - Reilly_2005_J.Lipid.Res_46_1914
Author(s) : Reilly MP , Foulkes AS , Wolfe ML , Rader DJ
Ref : J Lipid Res , 46 :1914 , 2005
Abstract :

Lipoprotein lipase, HL, and endothelial lipase (EL) are proteoglycan-bound enzymes that regulate plasma lipoprotein levels through coordinated triglyceride (TG) lipase and phospholipase activity. We hypothesized that single nucleotide polymorphisms (SNPs) in lipase genes would have higher order impact on plasma lipoproteins beyond the influence of individual SNPs. In a sample of asymptomatic Caucasian subjects (n = 738), we used a two-stage approach, first identifying groups of subjects with similar multilocus lipase genotypes and then characterizing the relationships between genotype groups and plasma lipids. Using complementary methods, including a permutation test procedure and a mixed-effects modeling approach, we found a higher order interaction between four SNPs in three lipase genes (EL 2,237 3' untranslated region, EL Thr111Ile, HL -514C/T, and LPL HindIII) and plasma TG levels. Subjects who were heterozygous for all four lipase SNPs had significantly higher plasma TG levels beyond the effect of individual lipase SNPs and environmental factors, even after correcting for multiple comparisons. In conclusion, lipase genes had synergistic association with plasma TG beyond individual gene effects. Higher order multilocus genotype contributions to dyslipidemia and atherosclerotic cardiovascular disease need to be considered a priori because they may have an important effect even in the absence of significant main effects of the individual genes.

PubMedSearch : Reilly_2005_J.Lipid.Res_46_1914
PubMedID: 15961789

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Citations formats

Reilly MP, Foulkes AS, Wolfe ML, Rader DJ (2005)
Higher order lipase gene association with plasma triglycerides
J Lipid Res 46 :1914

Reilly MP, Foulkes AS, Wolfe ML, Rader DJ (2005)
J Lipid Res 46 :1914