Microsomal triglyceride transfer protein -164 T > C gene polymorphism and risk of cardiovascular disease: results from the EPIC-Potsdam case-cohort study

BMC Medical Genetics

Research Article

Eva Fisher¹  Beate Weikert²  Heiner Boeing³  Maria Arregui³  Sven Knüppel³  Brian Buijsse³  Romina di Giuseppe³  Cornelia Weikert⁴  Andreas Fritsche⁵  Hans-Georg Joost⁶  Susanne Moebus⁷  Sonali Pechlivanis⁷  Stefan N Willich⁸ 

[1] Administrative Office of the Commission on Genetic Testing, Robert Koch-Institute, Berlin, Germany;Agency for Quality in Medicine, Berlin, Germany;Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany;Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany;Institute for Social Medicine, Epidemiology and Health Economics and Chairman, Charité Center 1 for Humanities and Health Sciences, Charité University Medical Center, Berlin, Germany;Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University of Tübingen, Tübingen, Germany;Department of Pharmacology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany;Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany;Institute for Social Medicine, Epidemiology and Health Economics and Chairman, Charité Center 1 for Humanities and Health Sciences, Charité University Medical Center, Berlin, Germany;

关键词: Epidemiology;    Genetics;    Myocardial infarction;    Ischemic stroke;    Cholesterol;    Additive interaction;   

DOI  :  10.1186/1471-2350-14-19

 received in 2012-08-09, accepted in 2013-01-23,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundThe microsomal triglyceride transfer protein (MTTP) is encoded by the MTTP gene that is regulated by cholesterol in humans. Previous studies investigating the effect of MTTP on ischemic heart disease have produced inconsistent results. Therefore, we have tested the hypothesis that the rare allele of the -164T > C polymorphism in MTTP alters the risk of cardiovascular disease (CVD), depending on the cholesterol levels.MethodsThe -164T > C polymorphism was genotyped in a case-cohort study (193 incident myocardial infarction (MI) and 131 incident ischemic stroke (IS) cases and 1 978 non-cases) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam study, comprising 27 548 middle-aged subjects. The Heinz Nixdorf Recall study (30 CVD cases and 1 188 controls) was used to replicate our findings.ResultsGenotype frequencies were not different between CVD and CVD free subjects (P = 0.79). We observed an interaction between the -164T > C polymorphism and total cholesterol levels in relation to future CVD. Corresponding stratified analyses showed a significant increased risk of CVD (HRadditve = 1.38, 95% CI: 1.07 to 1.78) for individuals with cholesterol levels <200 mg/dL in the EPIC-Potsdam study. HRadditive was 1.06, 95% CI: 0.33 to 3.40 for individuals in the Heinz Nixdorf Recall study. A borderline significant decrease in CVD risk was observed in subjects with cholesterol levels ≥200 mg/dL (HRadditve = 0.77, 95% CI: 0.58 to 1.03) in the EPIC-Potsdam study. A similar trend was observed in the independent cohort (HRadditve = 0.60, 95% CI: 0.29 to 1.25).ConclusionsOur study suggests an interaction between MTTP -164T > C functional polymorphism with total cholesterol levels. Thereby risk allele carriers with low cholesterol levels may be predisposed to an increased risk of developing CVD, which seems to be abolished among risk allele carriers with high cholesterol levels.

【 授权许可】

CC BY   
© di Giuseppe et al.; licensee BioMed Central Ltd. 2013