Higher order lipase gene association with plasma triglycerides
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 impa...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2005-09-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520329382 |
| _version_ | 1818728291802021888 |
|---|---|
| author | Muredach P. Reilly Andrea S. Foulkes Megan L. Wolfe Daniel J. Rader |
| author_facet | Muredach P. Reilly Andrea S. Foulkes Megan L. Wolfe Daniel J. Rader |
| author_sort | Muredach P. Reilly |
| collection | DOAJ |
| description | 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 Hind III) 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. |
| first_indexed | 2024-12-17T22:27:40Z |
| format | Article |
| id | doaj.art-7f583d250d714ee59fe9b4a06ff410e6 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T22:27:40Z |
| publishDate | 2005-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-7f583d250d714ee59fe9b4a06ff410e62022-12-21T21:30:19ZengElsevierJournal of Lipid Research0022-22752005-09-0146919141922Higher order lipase gene association with plasma triglyceridesMuredach P. Reilly0Andrea S. Foulkes1Megan L. Wolfe2Daniel J. Rader3To whom correspondence should be addressed.; Cardiovascular Division and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PADepartment of Biostatistics, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MACardiovascular Division and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PACardiovascular Division and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PALipoprotein 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 Hind III) 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.http://www.sciencedirect.com/science/article/pii/S0022227520329382lipoproteinslipaseshigher order gene interactions |
| spellingShingle | Muredach P. Reilly Andrea S. Foulkes Megan L. Wolfe Daniel J. Rader Higher order lipase gene association with plasma triglycerides Journal of Lipid Research lipoproteins lipases higher order gene interactions |
| title | Higher order lipase gene association with plasma triglycerides |
| title_full | Higher order lipase gene association with plasma triglycerides |
| title_fullStr | Higher order lipase gene association with plasma triglycerides |
| title_full_unstemmed | Higher order lipase gene association with plasma triglycerides |
| title_short | Higher order lipase gene association with plasma triglycerides |
| title_sort | higher order lipase gene association with plasma triglycerides |
| topic | lipoproteins lipases higher order gene interactions |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520329382 |
| work_keys_str_mv | AT muredachpreilly higherorderlipasegeneassociationwithplasmatriglycerides AT andreasfoulkes higherorderlipasegeneassociationwithplasmatriglycerides AT meganlwolfe higherorderlipasegeneassociationwithplasmatriglycerides AT danieljrader higherorderlipasegeneassociationwithplasmatriglycerides |