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




Microsomal triglyceride transfer protein -164 T > C gene polymorphism and risk of cardiovascular disease: results from the EPIC-Potsdam case-cohort study - Download this document for free, or read online. Document in PDF available to download.

BMC Medical Genetics

, 14:19

Genetic epidemiology and genetic associations

Abstract

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.

KeywordsEpidemiology Genetics Myocardial infarction Ischemic stroke Cholesterol Additive interaction  Download fulltext PDF



Author: Romina di Giuseppe - Sonali Pechlivanis - Eva Fisher - Maria Arregui - Beate Weikert - Sven Knüppel - Brian Buijsse - Andr

Source: https://link.springer.com/



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