Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Factor VII, blood lipids and fat intake: gene–nutrient interaction and risk of coronary heart disease with the factor VII R353Q polymorphism

Abstract

Background: The relation between dietary fat, blood lipids, plasma factor VII coagulant activity (FVIIc) and risk of coronary heart disease (CHD) according to the R353Q polymorphism in the factor VII gene was assessed.

Methods: Cross-sectional study of 15 073 individuals participating in the European Prospective Investigation of Cancer (EPIC) Norfolk, 7433 of which had FVIIc available. Nested case–control study of 985 CHD cases and 2009 matched controls.

Results: FVIIc was significantly associated with total fat intake in females, especially in the RR homozygotes (standardized β=0.24; 95% confidence interval (95% CI) 0.08–0.40; P<0.01), but there were no associations with intakes of saturated, monounsaturated or polyunsaturated fatty acids according to genotype and no associations in males. FVIIc was significantly positively associated with total cholesterol (P<0.01) and with triacylglycerol (P<0.001) in both genders, with an interaction according to genotype for triacylglycerol in males: β Q allele carriers 0.26 (95% CI 0.18–0.34), β RR homozygotes 0.16 (95% CI 0.12–0.20) (Z interaction =−2.24; P<0.05). There was no effect of genotype on the odds ratio (OR) for incident CHD: OR 0.89 for Q allele carriers compared with RR homozygotes (95% CI 0.77–1.02) in 985 cases and 2009 matched controls.

Conclusion: These results show a strong association between dietary fat intake and FVIIc in women, and between serum triacylglycerol and cholesterol and FVIIc levels in both genders. The R353Q genotype only marginally affected modulation of FVIIc by dietary fat. The association between triacylglycerol and FVIIc was significantly stronger in males carrying the Q allele than in those with the RR genotype.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Allman-Farinelli MA, Gomes K, Favaloro EJ, Petocz P (2005). A diet rich in high-oleic acid sunflower oil favorably alters low-density lipoprotein cholesterol, triglycerides, and factor VII coagulant activity. J Am Diet Assoc 105, 1071–1079.

    Article  CAS  Google Scholar 

  2. Bingham SA, Welch AA, McTaggart A, Mulligan AA, Runswick SA, Luben R et al. (2001). Nutritional methods in the European prospective investigation of cancer in Norfolk. Public Health Nutr 4, 847–858.

    Article  CAS  Google Scholar 

  3. Day N, Oakes S, Luben R, Khaw KT, Bingham S, Welch A et al. (1999). EPIC-Norfolk: study design and characteristics of the cohort. European prospective investigation of cancer. Br J Cancer 80 (Suppl 1), 95–103.

    Google Scholar 

  4. Donati MB, Zito F, Castelnuovo AD, Iacoviello L (2000). Genes, coagulation and cardiovascular risk. J Hum Hypertens 14, 369–372.

    Article  CAS  Google Scholar 

  5. Feng D, Tofler GH, Larson MG, O'Donnell CJ, Lipinska I, Schmitz C et al. (2000). Factor VII gene polymorphism, factor VII levels, and prevalent cardiovascular disease: the Framingham Heart Study. Arterioscler Thromb Vasc Biol 20, 593–600.

    Article  CAS  Google Scholar 

  6. Friedewald WT, Levy RI, Fredrickson DS (1972). Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18, 499–502.

    CAS  Google Scholar 

  7. Girelli D, Russo C, Ferraresi P, Olivieri O, Pinotti M, Friso S et al. (2000). Polymorphisms in the factor VII gene and the risk of myocardial infarction in patients with coronary artery disease. N Engl J Med 343, 774–780.

    Article  CAS  Google Scholar 

  8. Green F, Kelleher C, Wilkes H, Temple A, Meade T, Humphries S (1991). A common genetic polymorphism associated with lower coagulation factor VII levels in healthy individuals. Arterioscler Thromb 11, 540–546.

    Article  CAS  Google Scholar 

  9. Hong Y, Pedersen NL, Egberg N, de Faire U (1999). Genetic effects for plasma factor VII levels independent of and in common with triglycerides. Thromb Haemost 81, 382–386.

    Article  CAS  Google Scholar 

  10. Humphries SE, Lane A, Dawson S, Green FR (1992). The study of gene-environment interactions that influence thrombosis and fibrinolysis. Genetic variation at the loci for factor VII and plasminogen activator inhibitor-1. Arch Pathol Lab Med 116, 1322–1329.

    CAS  PubMed  Google Scholar 

  11. Hunault M, Arbini AA, Lopaciuk S, Carew JA, Bauer KA (1997). The Arg353Gln polymorphism reduces the level of coagulation factor VII. In vivo and in vitro studies. Arterioscler Thromb Vasc Biol 17, 2825–2829.

    Article  CAS  Google Scholar 

  12. Iacoviello L, Di Castelnuovo A, D'Orazio A, Donati B (1999). Cigarette smoking doubles the risk of myocardial infarction in carriers of a protective polymorphism in the blood coagulation factor VII gene. Thromb Haemost 81, 658.

    CAS  PubMed  Google Scholar 

  13. Iacoviello L, Di Castelnuovo A, De Knijff P, D'Orazio A, Amore C, Arboretti R et al. (1998). Polymorphisms in the coagulation factor VII gene and the risk of myocardial infarction. N Engl J Med 338, 79–85.

    Article  CAS  Google Scholar 

  14. Junker R, Kratz M, Neufeld M, Erren M, Nofer JR, Schulte H et al. (2001). Effects of diets containing olive oil, sunflower oil, or rapeseed oil on the hemostatic system. Thromb Haemost 85, 280–286.

    Article  CAS  Google Scholar 

  15. Lane A, Green F, Scarabin PY, Nicaud V, Bara L, Humphries S et al. (1996). Factor VII Arg/Gln353 polymorphism determines factor VII coagulant activity in patients with myocardial infarction (MI) and control subjects in Belfast and in France but is not a strong indicator of MI risk in the ECTIM study. Atherosclerosis 119, 119–127.

    Article  CAS  Google Scholar 

  16. Larsen LF, Bladbjerg EM, Jespersen J, Marckmann P (1997). Effects of dietary fat quality and quantity on postprandial activation of blood coagulation factor VII. Arterioscler Thromb Vasc Biol 17, 2904–2909.

    Article  CAS  Google Scholar 

  17. Lindman AS, Muller H, Seljeflot I, Prydz H, Veierod M, Pedersen JI (2003). Effects of dietary fat quantity and composition on fasting and postprandial levels of coagulation factor VII and serum choline-containing phospholipids. Br J Nutr 90, 329–336.

    Article  CAS  Google Scholar 

  18. Lindman AS, Pedersen JI, Arnesen H, Hjerkinn EM, Veierod MB, Prydz H et al. (2004). Coagulation factor VII, R353Q polymorphism, and serum choline-containing phospholipids in males at high risk for coronary heart disease. Thromb Res 113, 57–65.

    Article  CAS  Google Scholar 

  19. Meade TW, Mellows S, Brozovic M, Miller GJ, Chakrabarti RR, North WR et al. (1986). Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 2, 533–537.

    Article  CAS  Google Scholar 

  20. Mennen LI, de Maat MP, Schouten EG, Kluft C, Witteman JC, Hofman A et al. (1998). Dietary effects on coagulation factor VII vary across genotypes of the R/Q353 polymorphism in elderly people. J Nutr 128, 870–874.

    Article  CAS  Google Scholar 

  21. Mennen LI, Witteman JC, den Breeijen JH, Schouten EG, de Jong PT, Hofman A et al. (1997). The association of dietary fat and fiber with coagulation factor VII in the elderly: the Rotterdam Study. Am J Clin Nutr 65, 732–736.

    Article  CAS  Google Scholar 

  22. Miller GJ, Cruickshank JK, Ellis LJ, Thompson RL, Wilkes HC, Stirling Y et al. (1989). Fat consumption and factor VII coagulant activity in middle-aged men. An association between a dietary and thrombogenic coronary risk factor. Atherosclerosis 78, 19–24.

    Article  CAS  Google Scholar 

  23. Miller GJ, Martin JC, Mitropoulos KA, Reeves BE, Thompson RL, Meade TW et al. (1991). Plasma factor VII is activated by postprandial triglyceridaemia, irrespective of dietary fat composition. Atherosclerosis 86, 163–171.

    Article  CAS  Google Scholar 

  24. Mitropoulos KA, Esnouf MP, Meade TW (1987). Increased factor VII coagulant activity in the rabbit following diet-induced hypercholesterolaemia. Evidence for increased conversion of VII to alpha VIIa and higher flux within the coagulation pathway. Atherosclerosis 63, 43–52.

    Article  CAS  Google Scholar 

  25. Pereira MA, O'Reilly E, Augustsson K, Fraser GE, Goldbourt U, Heitmann BL et al. (2004). Dietary fiber and risk of coronary heart disease: a pooled analysis of cohort studies. Arch Intern Med 164, 370–376.

    Article  Google Scholar 

  26. Roche HM, Gibney MJ (1997). Postprandial coagulation factor VII activity: the effect of monounsaturated fatty acids. Br J Nutr 77, 537–549.

    Article  CAS  Google Scholar 

  27. Ronaghi M, Karamohamed S, Pettersson B, Uhlen M, Nyren P (1996). Real-time DNA sequencing using detection of pyrophosphate release. Anal Biochem 242, 84–89.

    Article  CAS  Google Scholar 

  28. Sanders TA, de Grassi T, Miller GJ, Humphries SE (1999). Dietary oleic and palmitic acids and postprandial factor VII in middle-aged men heterozygous and homozygous for factor VII R353Q polymorphism. Am J Clin Nutr 69, 220–225.

    Article  CAS  Google Scholar 

  29. Sanders TA, de Grassi T, Miller GJ, Morrissey JH (2000). Influence of fatty acid chain length and cis/trans isomerization on postprandial lipemia and factor VII in healthy subjects (postprandial lipids and factor VII). Atherosclerosis 149, 413–420.

    Article  CAS  Google Scholar 

  30. Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S et al. (2007). Triglycerides and the risk of coronary heart disease: 10 158 incident cases among 262 525 participants in 29 Western prospective studies. Circulation 115, 450–458.

    Article  CAS  Google Scholar 

  31. Simpson HC, Mann JI, Meade TW, Chakrabarti R, Stirling Y, Woolf L (1983). Hypertriglyceridaemia and hypercoagulability. Lancet 1, 786–790.

    Article  CAS  Google Scholar 

  32. Wareham NJ, Jakes RW, Rennie KL, Schuit J, Mitchell J, Hennings S et al. (2003). Validity and repeatability of a simple index derived from the short physical activity questionnaire used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Public Health Nutr 6, 407–413.

    Article  Google Scholar 

  33. Welch AA, Luben R, Khaw KT, Bingham SA (2005). The CAFE computer program for nutritional analysis of the EPIC-Norfolk food frequency questionnaire and identification of extreme nutrient values. J Hum Nutr Diet 18, 99–116.

    Article  CAS  Google Scholar 

  34. Welch AA, McTaggart A, Mulligan AA, Luben R, Walker N, Khaw KT et al. (2001). DINER (Data Into Nutrients for Epidemiological Research)—a new data-entry program for nutritional analysis in the EPIC-Norfolk cohort and the 7-day diary method. Public Health Nutr 4, 1253–1265.

    Article  CAS  Google Scholar 

  35. Wu K, Bowman R, Welch AA, Luben RN, Wareham N, Khaw KT et al. (2007). Apolipoprotein E polymorphisms, dietary fat and fibre, and serum lipids: the EPIC Norfolk study. Eur Heart J 28, 2930–2936.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was funded by the Food Standards Agency and the Medical Research Council.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S A Bingham.

Additional information

Contributors: SAB, NJW and K-TK instigated the study methods and protocols and are Principal Investigators of EPIC Norfolk. RB was responsible for the genotyping. AMCPJ carried out the statistical analysis. RNL was responsible for collection and analysis of end point and other data. AAW was responsible for collection and nutritional analysis of data. AMCPJ and RB wrote the paper, with contributions from all other authors. None of the authors had any conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bowman, R., Joosen, A., Welch, A. et al. Factor VII, blood lipids and fat intake: gene–nutrient interaction and risk of coronary heart disease with the factor VII R353Q polymorphism. Eur J Clin Nutr 63, 771–777 (2009). https://doi.org/10.1038/ejcn.2008.28

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2008.28

Keywords

This article is cited by

Search

Quick links