The −250G>A Promoter Variant in Hepatic Lipase Associates with Elevated Fasting Serum High-Density Lipoprotein Cholesterol Modulated by Interaction with Physical Activity in a Study of 16,156 Danish Subjects
Abstract
Context: Hepatic lipase plays a pivotal role in the metabolism of high-density lipoprotein (HDL) and low-density lipoprotein by involvement in reverse cholesterol transport and the formation of atherogenic small dense low-density lipoprotein. Objectives: The objective was to investigate the impact of variants in LIPC on metabolic traits and type 2 diabetes in a large sample of Danes. Because behavioral factors influence hepatic lipase activity, we furthermore examined possible gene-environment interactions in the population-based Inter99 study. Design: The LIPC −250G>A (rs2070895) variant was genotyped in the Inter99 study (n = 6070), the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care Denmark screening cohort of individuals with risk factors for undiagnosed type 2 diabetes (n = 8662), and in additional type 2 diabetic patients (n = 1,064) and glucose-tolerant control subjects (n = 360). Results: In the Inter99 study, the A allele of rs2070895 associated with a 0.057 mmol/liter [95% confidence interval (CI) 0.039–0.075] increase in fasting serum HDL-cholesterol (HDL-c) (P = 8 × 10−10) supported by association in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care study [0.038 mmol/liter per allele (95% CI 0.024–0.053); P = 2 × 10−7). The allelic effect on HDL-c was modulated by interaction with self-reported physical activity (Pinteraction = 0.002) because vigorous physically active homozygous A-allele carriers had a 0.30 mmol/liter (95% CI 0.22–0.37) increase in HDL-c compared with homozygous G-allele carriers. Conclusions: We validate the association of LIPC promoter variation with fasting serum HDL-c and present data supporting an interaction with physical activity implying an increased effect on HDL-c in vigorous physically active subjects carrying the −250 A allele. This interaction may have potential implications for public health and disease prevention.
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The variant rs10468017 influences LIPC expression and serum HDL levels.
“a functional promoter variant, rs10468017, (*P* = 1.34e-08), that influences LIPC expression and serum HDL levels”
From Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene ( <i>LIPC</i> ) (2010) · cites this paper as [24]
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- Authors
- Grarup, N., Andreasen, C. H., Andersen, M. K., Albrechtsen, A., Sandbæk, A., Lauritzen, T., Borch-Johnsen, K., Jørgensen, T., Schmitz, O., Hansen, T., & Pedersen, O.
- Affiliations
- Steno Diabetes Centers (DK)
- University of Helsinki (FI)
- University of Copenhagen (DK)
- Aarhus University (DK)
- Faculty of Health Sciences (K.B-J., O.P.), University of Aarhus, DK-8000 Aarhus, Denmark
- Glostrup Hospital (DK)
- Corresponding author
- Grarup, Niels
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2008-06-01
- Volume
- 93
- Issue
- 6
- Pages
- 2294-2299
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2029115254
- Cited by
- 34
- References
- 38
- Citations by year
- 2023: 2 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 2 · 2013: 3 · 2012: 1
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- hepatic lipase, HDL cholesterol, physical activity, gene-environment interaction, type 2 diabetes, genetic association, reverse cholesterol transport, Danish population
- MeSH terms
- Denmark, Diabetes Mellitus, Type 2, Fasting, Genetic Testing, Genotype, Heterozygote, Humans, Insulin Resistance, Lipase, Cholesterol, HDL, Motor Activity, Promoter Regions, Genetic, Cohort Studies, Linkage Disequilibrium, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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