Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
BMC Med Genet. 2013 Jan 29;14:19. doi: 10.1186/1471-2350-14-19.
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.
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.
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).
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.
微粒体甘油三酯转移蛋白（MTTP）由 MTTP 基因编码，该基因在人类中受胆固醇调控。先前研究 MTTP 对缺血性心脏病影响的结果并不一致。因此，我们检验了假设，即 MTTP 基因-164T＞C 多态性的罕见等位基因改变了心血管疾病（CVD）的风险，这取决于胆固醇水平。
在嵌套于欧洲癌症前瞻性调查与营养（EPIC）-波茨坦研究的病例-对照研究（193 例心肌梗死（MI）和 131 例缺血性卒中（IS）病例和 1978 例非病例）中，对-164T＞C 多态性进行了基因分型。Heinz Nixdorf 回顾性研究（30 例 CVD 病例和 1188 例对照）用于复制我们的发现。
CVD 病例和无 CVD 病例的基因型频率无差异（P=0.79）。我们观察到-164T＞C 多态性与总胆固醇水平之间存在交互作用，与未来 CVD 相关。相应的分层分析显示，在 EPIC-Potsdam 研究中，胆固醇水平＜200mg/dL 的个体 CVD 风险显著增加（HR（相加）=1.38，95%CI：1.07-1.78）。Heinz Nixdorf 回顾性研究中 HR（相加）为 1.06，95%CI：0.33-3.40。在 EPIC-Potsdam 研究中，胆固醇水平≥200mg/dL 的个体中 CVD 风险呈临界下降趋势（HR（相加）=0.77，95%CI：0.58-1.03）。在独立队列中也观察到类似的趋势（HR（相加）=0.60，95%CI：0.29-1.25）。
我们的研究表明，MTTP-164T＞C 功能性多态性与总胆固醇水平之间存在相互作用。因此，低胆固醇水平的风险等位基因携带者可能易患 CVD 风险增加，而高胆固醇水平的风险等位基因携带者似乎可以消除这种风险。
