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首页> 外文期刊>BMC Medical Genomics >Fatty acid binding protein 3 ( fabp3 ) is associated with insulin, lipids and cardiovascular phenotypes of the metabolic syndrome through epigenetic modifications in a northern european family population
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Fatty acid binding protein 3 ( fabp3 ) is associated with insulin, lipids and cardiovascular phenotypes of the metabolic syndrome through epigenetic modifications in a northern european family population

机译：脂肪酸结合蛋白3（Fabp3）与代谢综合征的胰岛素，脂质和心血管表型通过北欧家族中的表观遗传修饰相关

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Background Fatty acid-binding proteins (FABPs) play regulatory roles at the nexus of lipid metabolism and signaling. Dyslipidemia in clinical manifestation frequently co-occurs with obesity, insulin resistance and hypertension in the Metabolic Syndrome (MetS). Animal studies have suggested FABPs play regulatory roles in expressing MetS phenotypes. In our family cohort of Northern European descent, transcript levels in peripheral white blood cells (PWBCs) of a key FABPs, FABP3, is correlated with the MetS leading components. However, evidence supporting the functions of FABPs in humans using genetic approaches has been scarce, suggesting FABPs may be under epigenetic regulation. The objective of this study was to test the hypothesis that CpG methylation status of a key regulator of lipid homeostasis, FABP3 , is a quantitative trait associated with status of MetS phenotypes in humans. Methods We used a mass-spec based quantitative method, EpiTYPER ? , to profile a CpG island that extends from the promoter to the first exon of the FABP3 gene in our family-based cohort of Northern European descent (n=517). We then conducted statistical analysis of the quantitative relationship of CpG methylation and MetS measures following the variance-component association model. Heritability of each methylation and the effect of age and sex on CpG methylation were also assessed in our families. Results We find that methylation levels of individual CpG units and the regional average are heritable and significantly influenced by age and sex. Regional methylation was strongly associated with plasma total cholesterol (p=0.00028) and suggestively associated with LDL-cholesterol (p=0.00495). Methylation at individual units was significantly associated with insulin sensitivity, lipid particle sizing and diastolic blood pressure (pWHR = ?0.72; βLDL-c = ?0.53) while positively correlated with plasma adiponectin (β=0.24). Further, we show that differential methylation of FABP3 affects binding activity with nuclear proteins from heart tissue. This region that we found under methylation regulation overlaps with a region actively modified by histone codes in the newly available ENCODE data. Conclusions Our findings suggest that DNA methylation of FABP3 strongly influences MetS, and this may have important implications for cardiovascular disease.
机译：背景脂肪酸结合蛋白（FABPS）在脂质代谢和信号传导的Nexus下发挥调节作用。临床表现的血脂血症经常在代谢综合征（Mets）中的肥胖，胰岛素抵抗和高血压常常进行。动物研究表明FABPS发挥调节作用表达METS表型。在我们的北欧血液群组中，关键织物的外周白细胞（PWBC）的转录物水平与METS领先组件相关。然而，支持使用遗传方法支持人类Fabps功能的证据已经是稀缺的，表明FABPS可能属于表观遗传调控。本研究的目的是测试脂质稳态，Fabp3的关键调节器的CpG甲基化状态是与人类在人类表型的状态相关的定量性状。方法采用了基于批次的定量方法，Epiteper吗？ ，将从促进者延伸到我们家庭的北欧血统队列（n = 517）的FABP3基因的第一个外显子的CPG岛。然后，我们对方差 - 组分关联模型进行了对CpG甲基化的定量关系的统计分析。在我们的家庭中还评估了每种甲基化和年龄和性别对CpG甲基化的遗传性的遗传性。结果我们发现个体CPG单位和区域平均水平的甲基化水平是遗传性和受年龄和性别的显着影响。区域甲基化与血浆总胆固醇（P = 0.00028）强烈相关，并暗示与LDL-胆固醇相关（P = 0.00495）。单位单位的甲基化与胰岛素敏感性显着相关，脂粒子尺寸和舒张压（PWHR = 0.72;β<亚> LDL-C =？0.53），同时与血浆脂联素正相关（ β= 0.24）。此外，我们表明Fabp3的差异甲基化影响来自心脏组织的核蛋白质的结合活性。我们在甲基化调节下发现的该区域与新可用的编码数据中的组蛋白代码主动修改的区域重叠。结论我们的研究结果表明FABP3的DNA甲基化强烈影响METS，这可能对心血管疾病具有重要意义。

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