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

• Main Authors: di Giuseppe Romina (Author), Pechlivanis Sonali (Author), Fisher Eva (Author), Arregui Maria (Author), Weikert Beate (Author), Knüppel Sven (Author), Buijsse Brian (Author), Fritsche Andreas (Author), Willich Stefan N (Author), Joost Hans-Georg (Author), Boeing Heiner (Author), Moebus Susanne (Author), Weikert Cornelia (Author)
• Format: Book
• Published: BMC, 2013-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<p>Abstract</p> <p>Background</p> <p>The microsomal triglyceride transfer protein (MTTP) is encoded by the <it>MTTP</it> gene that is regulated by cholesterol in humans. Previous studies investigating the effect of <it>MTTP</it> on ischemic heart disease have produced inconsistent results. Therefore, we have tested the hypothesis that the rare allele of the -164T > C polymorphism in <it>MTTP</it> alters the risk of cardiovascular disease (CVD), depending on the cholesterol levels.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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).</p> <p>Conclusions</p> <p>Our study suggests an interaction between <it>MTTP</it> -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.</p>

Item Description

10.1186/1471-2350-14-19
1471-2350