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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.

bmc medical genetics

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