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Hepatic Lipase, Genetically Elevated High-Density Lipoprotein, and Risk of Ischemic Cardiovascular Disease

Context: Hepatic lipase influences metabolism of high-density lipoprotein (HDL), a risk factor for ischemic cardiovascular disease (ICD: ischemic heart disease and ischemic cerebrovascular disease). Objective: We tested the hypothesis that genetic variation in the hepatic lipase genetic variants V73... Full description

Journal Title: The journal of clinical endocrinology and metabolism 2009-04, Vol.94 (4), p.1264-1273
Main Author: Johannsen, Trine Holm
Other Authors: Kamstrup, Pia R , Andersen, Rolf V , Jensen, Gorm B , Sillesen, Henrik , Tybjærg-Hansen, Anne , Nordestgaard, Børge G
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Bethesda, MD: Endocrine Society
ID: ISSN: 0021-972X
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title: Hepatic Lipase, Genetically Elevated High-Density Lipoprotein, and Risk of Ischemic Cardiovascular Disease
format: Article
creator:
  • Johannsen, Trine Holm
  • Kamstrup, Pia R
  • Andersen, Rolf V
  • Jensen, Gorm B
  • Sillesen, Henrik
  • Tybjærg-Hansen, Anne
  • Nordestgaard, Børge G
subjects:
  • Abridged Index Medicus
  • Adult
  • Amino Acid Substitution
  • Biological and medical sciences
  • Cardiovascular Diseases - epidemiology
  • Cardiovascular Diseases - genetics
  • Cerebral Hemorrhage - epidemiology
  • Cerebral Hemorrhage - genetics
  • Cholesterol, HDL - blood
  • Cholesterol, HDL - genetics
  • Denmark - epidemiology
  • Endocrinopathies
  • Feeding. Feeding behavior
  • Female
  • Fundamental and applied biological sciences. Psychology
  • Genetic Carrier Screening
  • Genetic Variation
  • Humans
  • Lipase - blood
  • Lipase - genetics
  • Lipoproteins, HDL - blood
  • Lipoproteins, HDL - genetics
  • Male
  • Medical sciences
  • Middle Aged
  • Myocardial Infarction - epidemiology
  • Myocardial Infarction - genetics
  • Myocardial Ischemia - blood
  • Myocardial Ischemia - genetics
  • Risk Factors
  • Stroke - blood
  • Stroke - genetics
  • Vertebrates: anatomy and physiology, studies on body, several organs or systems
  • Vertebrates: endocrinology
ispartof: The journal of clinical endocrinology and metabolism, 2009-04, Vol.94 (4), p.1264-1273
description: Context: Hepatic lipase influences metabolism of high-density lipoprotein (HDL), a risk factor for ischemic cardiovascular disease (ICD: ischemic heart disease and ischemic cerebrovascular disease). Objective: We tested the hypothesis that genetic variation in the hepatic lipase genetic variants V73M, N193S, S267F, L334F, T383M, and −480c>t influence levels of lipids, lipoproteins, and apolipoproteins and risk of ICD. Design: For the cross-sectional study, we genotyped 9003 individuals from the Copenhagen City Heart Study; hereof were 8971 individuals included in the prospective study, 1747 of whom had incident ICD during 28 yr of follow-up. For the case-control studies, 2110 ischemic heart disease patients vs. 4899 controls and 769 ischemic cerebrovascular disease patients vs. 2836 controls, respectively, were genotyped. Follow-up was 100% complete. Results: HDL cholesterol was higher by 0.21 mmol/liter in S267F heterozygotes, by 0.06 mmol/liter in −480c>t heterozygotes, and by 0.13 mmol/liter in −480c>t homozygotes, as compared with noncarriers. These HDL increases theoretically predicted hazard ratios for ICD of 0.87 [95% confidence interval (CI) 0.84–0.90], 0.96 (95% CI 0.95–0.97), and 0.91 (95% CI 0.89–0.94), respectively; this calculation assumes that genetically elevated HDL levels confer decreased risk similar to common HDL elevations. In contrast, when all cases and controls were combined, the observed odds ratios for ICD for these three genetic variants vs. noncarriers were 1.19 (0.76–1.88), 1.04 (0.96–1.13), and 1.08 (0.89–1.30), respectively. Hazard/odds ratios for ICD in carriers vs. noncarriers of the four remaining hepatic lipase genetic variants did not differ consistently from 1.0. Conclusion: Hepatic lipase genetic variants with elevated levels of HDL cholesterol did not associate with risk of ICD. Hepatic lipase genetic variants with elevated levels of HDL cholesterol did not associate with risk of ischemic cardiovascular disease.
language: eng
source:
identifier: ISSN: 0021-972X
fulltext: no_fulltext
issn:
  • 0021-972X
  • 1945-7197
url: Link


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titleHepatic Lipase, Genetically Elevated High-Density Lipoprotein, and Risk of Ischemic Cardiovascular Disease
creatorJohannsen, Trine Holm ; Kamstrup, Pia R ; Andersen, Rolf V ; Jensen, Gorm B ; Sillesen, Henrik ; Tybjærg-Hansen, Anne ; Nordestgaard, Børge G
creatorcontribJohannsen, Trine Holm ; Kamstrup, Pia R ; Andersen, Rolf V ; Jensen, Gorm B ; Sillesen, Henrik ; Tybjærg-Hansen, Anne ; Nordestgaard, Børge G
descriptionContext: Hepatic lipase influences metabolism of high-density lipoprotein (HDL), a risk factor for ischemic cardiovascular disease (ICD: ischemic heart disease and ischemic cerebrovascular disease). Objective: We tested the hypothesis that genetic variation in the hepatic lipase genetic variants V73M, N193S, S267F, L334F, T383M, and −480c>t influence levels of lipids, lipoproteins, and apolipoproteins and risk of ICD. Design: For the cross-sectional study, we genotyped 9003 individuals from the Copenhagen City Heart Study; hereof were 8971 individuals included in the prospective study, 1747 of whom had incident ICD during 28 yr of follow-up. For the case-control studies, 2110 ischemic heart disease patients vs. 4899 controls and 769 ischemic cerebrovascular disease patients vs. 2836 controls, respectively, were genotyped. Follow-up was 100% complete. Results: HDL cholesterol was higher by 0.21 mmol/liter in S267F heterozygotes, by 0.06 mmol/liter in −480c>t heterozygotes, and by 0.13 mmol/liter in −480c>t homozygotes, as compared with noncarriers. These HDL increases theoretically predicted hazard ratios for ICD of 0.87 [95% confidence interval (CI) 0.84–0.90], 0.96 (95% CI 0.95–0.97), and 0.91 (95% CI 0.89–0.94), respectively; this calculation assumes that genetically elevated HDL levels confer decreased risk similar to common HDL elevations. In contrast, when all cases and controls were combined, the observed odds ratios for ICD for these three genetic variants vs. noncarriers were 1.19 (0.76–1.88), 1.04 (0.96–1.13), and 1.08 (0.89–1.30), respectively. Hazard/odds ratios for ICD in carriers vs. noncarriers of the four remaining hepatic lipase genetic variants did not differ consistently from 1.0. Conclusion: Hepatic lipase genetic variants with elevated levels of HDL cholesterol did not associate with risk of ICD. Hepatic lipase genetic variants with elevated levels of HDL cholesterol did not associate with risk of ischemic cardiovascular disease.
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subjectAbridged Index Medicus ; Adult ; Amino Acid Substitution ; Biological and medical sciences ; Cardiovascular Diseases - epidemiology ; Cardiovascular Diseases - genetics ; Cerebral Hemorrhage - epidemiology ; Cerebral Hemorrhage - genetics ; Cholesterol, HDL - blood ; Cholesterol, HDL - genetics ; Denmark - epidemiology ; Endocrinopathies ; Feeding. Feeding behavior ; Female ; Fundamental and applied biological sciences. Psychology ; Genetic Carrier Screening ; Genetic Variation ; Humans ; Lipase - blood ; Lipase - genetics ; Lipoproteins, HDL - blood ; Lipoproteins, HDL - genetics ; Male ; Medical sciences ; Middle Aged ; Myocardial Infarction - epidemiology ; Myocardial Infarction - genetics ; Myocardial Ischemia - blood ; Myocardial Ischemia - genetics ; Risk Factors ; Stroke - blood ; Stroke - genetics ; Vertebrates: anatomy and physiology, studies on body, several organs or systems ; Vertebrates: endocrinology
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2Andersen, Rolf V
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4Sillesen, Henrik
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6Nordestgaard, Børge G
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descriptionContext: Hepatic lipase influences metabolism of high-density lipoprotein (HDL), a risk factor for ischemic cardiovascular disease (ICD: ischemic heart disease and ischemic cerebrovascular disease). Objective: We tested the hypothesis that genetic variation in the hepatic lipase genetic variants V73M, N193S, S267F, L334F, T383M, and −480c>t influence levels of lipids, lipoproteins, and apolipoproteins and risk of ICD. Design: For the cross-sectional study, we genotyped 9003 individuals from the Copenhagen City Heart Study; hereof were 8971 individuals included in the prospective study, 1747 of whom had incident ICD during 28 yr of follow-up. For the case-control studies, 2110 ischemic heart disease patients vs. 4899 controls and 769 ischemic cerebrovascular disease patients vs. 2836 controls, respectively, were genotyped. Follow-up was 100% complete. Results: HDL cholesterol was higher by 0.21 mmol/liter in S267F heterozygotes, by 0.06 mmol/liter in −480c>t heterozygotes, and by 0.13 mmol/liter in −480c>t homozygotes, as compared with noncarriers. These HDL increases theoretically predicted hazard ratios for ICD of 0.87 [95% confidence interval (CI) 0.84–0.90], 0.96 (95% CI 0.95–0.97), and 0.91 (95% CI 0.89–0.94), respectively; this calculation assumes that genetically elevated HDL levels confer decreased risk similar to common HDL elevations. In contrast, when all cases and controls were combined, the observed odds ratios for ICD for these three genetic variants vs. noncarriers were 1.19 (0.76–1.88), 1.04 (0.96–1.13), and 1.08 (0.89–1.30), respectively. Hazard/odds ratios for ICD in carriers vs. noncarriers of the four remaining hepatic lipase genetic variants did not differ consistently from 1.0. Conclusion: Hepatic lipase genetic variants with elevated levels of HDL cholesterol did not associate with risk of ICD. Hepatic lipase genetic variants with elevated levels of HDL cholesterol did not associate with risk of ischemic cardiovascular disease.
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2Amino Acid Substitution
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4Cardiovascular Diseases - epidemiology
5Cardiovascular Diseases - genetics
6Cerebral Hemorrhage - epidemiology
7Cerebral Hemorrhage - genetics
8Cholesterol, HDL - blood
9Cholesterol, HDL - genetics
10Denmark - epidemiology
11Endocrinopathies
12Feeding. Feeding behavior
13Female
14Fundamental and applied biological sciences. Psychology
15Genetic Carrier Screening
16Genetic Variation
17Humans
18Lipase - blood
19Lipase - genetics
20Lipoproteins, HDL - blood
21Lipoproteins, HDL - genetics
22Male
23Medical sciences
24Middle Aged
25Myocardial Infarction - epidemiology
26Myocardial Infarction - genetics
27Myocardial Ischemia - blood
28Myocardial Ischemia - genetics
29Risk Factors
30Stroke - blood
31Stroke - genetics
32Vertebrates: anatomy and physiology, studies on body, several organs or systems
33Vertebrates: endocrinology
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titleHepatic Lipase, Genetically Elevated High-Density Lipoprotein, and Risk of Ischemic Cardiovascular Disease
authorJohannsen, Trine Holm ; Kamstrup, Pia R ; Andersen, Rolf V ; Jensen, Gorm B ; Sillesen, Henrik ; Tybjærg-Hansen, Anne ; Nordestgaard, Børge G
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33Vertebrates: endocrinology
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abstractContext: Hepatic lipase influences metabolism of high-density lipoprotein (HDL), a risk factor for ischemic cardiovascular disease (ICD: ischemic heart disease and ischemic cerebrovascular disease). Objective: We tested the hypothesis that genetic variation in the hepatic lipase genetic variants V73M, N193S, S267F, L334F, T383M, and −480c>t influence levels of lipids, lipoproteins, and apolipoproteins and risk of ICD. Design: For the cross-sectional study, we genotyped 9003 individuals from the Copenhagen City Heart Study; hereof were 8971 individuals included in the prospective study, 1747 of whom had incident ICD during 28 yr of follow-up. For the case-control studies, 2110 ischemic heart disease patients vs. 4899 controls and 769 ischemic cerebrovascular disease patients vs. 2836 controls, respectively, were genotyped. Follow-up was 100% complete. Results: HDL cholesterol was higher by 0.21 mmol/liter in S267F heterozygotes, by 0.06 mmol/liter in −480c>t heterozygotes, and by 0.13 mmol/liter in −480c>t homozygotes, as compared with noncarriers. These HDL increases theoretically predicted hazard ratios for ICD of 0.87 [95% confidence interval (CI) 0.84–0.90], 0.96 (95% CI 0.95–0.97), and 0.91 (95% CI 0.89–0.94), respectively; this calculation assumes that genetically elevated HDL levels confer decreased risk similar to common HDL elevations. In contrast, when all cases and controls were combined, the observed odds ratios for ICD for these three genetic variants vs. noncarriers were 1.19 (0.76–1.88), 1.04 (0.96–1.13), and 1.08 (0.89–1.30), respectively. Hazard/odds ratios for ICD in carriers vs. noncarriers of the four remaining hepatic lipase genetic variants did not differ consistently from 1.0. Conclusion: Hepatic lipase genetic variants with elevated levels of HDL cholesterol did not associate with risk of ICD. Hepatic lipase genetic variants with elevated levels of HDL cholesterol did not associate with risk of ischemic cardiovascular disease.
copBethesda, MD
pubEndocrine Society
pmid19088157
doi10.1210/jc.2008-1342
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