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Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies.

Publication ,  Journal Article
Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration, ; Sarwar, N; Sandhu, MS; Ricketts, SL; Butterworth, AS ...
Published in: Lancet
May 8, 2010

BACKGROUND: Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality. METHODS: We assessed the -1131T>C (rs662799) promoter polymorphism of the apolipoprotein A5 (APOA5) gene in relation to triglyceride concentration, several other risk factors, and risk of coronary heart disease. We compared disease risk for genetically-raised triglyceride concentration (20,842 patients with coronary heart disease, 35,206 controls) with that recorded for equivalent differences in circulating triglyceride concentration in prospective studies (302 430 participants with no history of cardiovascular disease; 12,785 incident cases of coronary heart disease during 2.79 million person-years at risk). We analysed -1131T>C in 1795 people without a history of cardiovascular disease who had information about lipoprotein concentration and diameter obtained by nuclear magnetic resonance spectroscopy. FINDINGS: The minor allele frequency of -1131T>C was 8% (95% CI 7-9). -1131T>C was not significantly associated with several non-lipid risk factors or LDL cholesterol, and it was modestly associated with lower HDL cholesterol (mean difference per C allele 3.5% [95% CI 2.6-4.6]; 0.053 mmol/L [0.039-0.068]), lower apolipoprotein AI (1.3% [0.3-2.3]; 0.023 g/L [0.005-0.041]), and higher apolipoprotein B (3.2% [1.3-5.1]; 0.027 g/L [0.011-0.043]). By contrast, for every C allele inherited, mean triglyceride concentration was 16.0% (95% CI 12.9-18.7), or 0.25 mmol/L (0.20-0.29), higher (p=4.4x10(-24)). The odds ratio for coronary heart disease was 1.18 (95% CI 1.11-1.26; p=2.6x10(-7)) per C allele, which was concordant with the hazard ratio of 1.10 (95% CI 1.08-1.12) per 16% higher triglyceride concentration recorded in prospective studies. -1131T>C was significantly associated with higher VLDL particle concentration (mean difference per C allele 12.2 nmol/L [95% CI 7.7-16.7]; p=9.3x10(-8)) and smaller HDL particle size (0.14 nm [0.08-0.20]; p=7.0x10(-5)), factors that could mediate the effects of triglyceride. INTERPRETATION: These data are consistent with a causal association between triglyceride-mediated pathways and coronary heart disease. FUNDING: British Heart Foundation, UK Medical Research Council, Novartis.

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Published In

Lancet

DOI

EISSN

1474-547X

Publication Date

May 8, 2010

Volume

375

Issue

9726

Start / End Page

1634 / 1639

Location

England

Related Subject Headings

  • Triglycerides
  • Risk Factors
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Particle Size
  • Mendelian Randomization Analysis
  • Lipoproteins, VLDL
  • Lipoproteins, LDL
  • Lipoproteins, HDL
  • Lipids
 

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Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration, ., Sarwar, N., Sandhu, M. S., Ricketts, S. L., Butterworth, A. S., Di Angelantonio, E., … Danesh, J. (2010). Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet, 375(9726), 1634–1639. https://doi.org/10.1016/S0140-6736(10)60545-4
Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration, John, Nadeem Sarwar, Manjinder S. Sandhu, Sally L. Ricketts, Adam S. Butterworth, Emanuele Di Angelantonio, S Matthijs Boekholdt, et al. “Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies.Lancet 375, no. 9726 (May 8, 2010): 1634–39. https://doi.org/10.1016/S0140-6736(10)60545-4.
Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration, Sarwar N, Sandhu MS, Ricketts SL, Butterworth AS, Di Angelantonio E, et al. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet. 2010 May 8;375(9726):1634–9.
Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration, John, et al. “Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies.Lancet, vol. 375, no. 9726, May 2010, pp. 1634–39. Pubmed, doi:10.1016/S0140-6736(10)60545-4.
Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration, Sarwar N, Sandhu MS, Ricketts SL, Butterworth AS, Di Angelantonio E, Boekholdt SM, Ouwehand W, Watkins H, Samani NJ, Saleheen D, Lawlor D, Reilly MP, Hingorani AD, Talmud PJ, Danesh J. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet. 2010 May 8;375(9726):1634–1639.
Journal cover image

Published In

Lancet

DOI

EISSN

1474-547X

Publication Date

May 8, 2010

Volume

375

Issue

9726

Start / End Page

1634 / 1639

Location

England

Related Subject Headings

  • Triglycerides
  • Risk Factors
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Particle Size
  • Mendelian Randomization Analysis
  • Lipoproteins, VLDL
  • Lipoproteins, LDL
  • Lipoproteins, HDL
  • Lipids