Key result
The LIPC -250G>A variant A allele was associated with a 0.057 mmol/liter increase in fasting HDL-cholesterol (P=8x10^-10), an effect amplified to 0.30 mmol/liter in vigorously active homozygotes.
Why the study?
Does the LIPC -250G>A variant and its interaction with physical activity affect fasting serum HDL-cholesterol in Danish subjects?
Observational (n=16,156)
Does the LIPC -250G>A variant and its interaction with physical activity affect fasting serum HDL-cholesterol in Danish subjects?
Effect estimate: 0.057 mmol/liter increase (95% CI 0.039-0.075)
p-value: p=8 x 10(-10)
The LIPC -250G>A promoter variant is associated with elevated fasting HDL-cholesterol, an effect that is significantly amplified by vigorous physical activity.
Observational data link LIPC variant to higher HDL amplified by activity; leaves open causal effects and practice implications.
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 x 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 x 10(-7)). The allelic effect on HDL-c was modulated by interaction with self-reported physical activity (P(interaction) = 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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Grarup et al. (2008) conducted an observational in Metabolic traits and type 2 diabetes (n=16,156). LIPC -250G>A (rs2070895) variant vs. G-allele carriers was evaluated on Fasting serum HDL-cholesterol (HDL-c) (0.057 mmol/liter increase, 95% CI 0.039-0.075, p=8 x 10(-10)). The LIPC -250G>A variant A allele was associated with a 0.057 mmol/liter increase in fasting HDL-cholesterol (P=8x10^-10), an effect amplified to 0.30 mmol/liter in vigorously active homozygotes.
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