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

Cornelia Weikert⁵  Susanne Moebus²  Heiner Boeing⁴  Hans-Georg Joost⁶  Stefan N Willich⁵  Andreas Fritsche⁷  Brian Buijsse⁴  Sven Knüppel⁴  Beate Weikert³  Maria Arregui⁴  Eva Fisher¹  Sonali Pechlivanis²  Romina di Giuseppe⁴ 

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

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

Others  :  1177734
DOI  :  10.1186/1471-2350-14-19

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

【 摘 要 】

Background

The 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.

Methods

The -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.

Results

Genotype 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 (HR_additve = 1.38, 95% CI: 1.07 to 1.78) for individuals with cholesterol levels <200 mg/dL in the EPIC-Potsdam study. HR_additive 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 (HR_additve = 0.77, 95% CI: 0.58 to 1.03) in the EPIC-Potsdam study. A similar trend was observed in the independent cohort (HR_additve = 0.60, 95% CI: 0.29 to 1.25).

Conclusions

Our 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】

   
2013 di Giuseppe et al.; licensee BioMed Central Ltd.

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