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首页> 外文期刊>Pharmacogenomics >An epigenome-wide association study of inflammatory response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network
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An epigenome-wide association study of inflammatory response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network

机译：脂质降低药物和饮食网络遗传学遗传学对泛料纤维炎症反应的外延一致性研究

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Aim: Fenofibrate, a PPAR-alpha inhibitor used for treating dyslipidemia, has well-documented anti-inflammatory effects that vary between individuals. While DNA sequence variation explains some of the observed variability in response, epigenetic patterns present another promising avenue of inquiry due to the biological links between the PPAR-alpha pathway, homocysteine and S-adenosylmethionine - a source of methyl groups for the DNA methylation reaction. Hypothesis: DNA methylation variation at baseline is associated with the inflammatory response to a short-term fenofibrate treatment. Methods: We have conducted the first epigenome-wide study of inflammatory response to daily treatment with 160 mg of micronized fenofibrate over a 3-week period in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n = 750). Epigenome-wide DNA methylation was quantified on CD4(+) T cells using the Illumina Infinium HumanMethylation450 array. Results: We identified multiple CpG sites significantly associated with the changes in plasma concentrations of inflammatory cytokines such as high sensitivity CRP (hsCRP, 7 CpG sites), IL-2 soluble receptor (IL-2sR, one CpG site), and IL-6 (4 CpG sites). Top CpG sites mapped to KIAA1324L (p = 2.63E-10), SMPD3 (p = 2.14E-08), SYNPO2 (p = 5.00E-08), ILF3 (p = 1.04E07), PRR3, GNL1 (p = 6.80E-09), FAM50B (p = 3.19E-08), RPTOR (p = 9.79e-07) and several intergenic regions (p < 1.03E-07). We also derived two inflammatory patterns using principal component analysis and uncovered additional epigenetic hits for each pattern before and after fenofibrate treatment. Conclusion: Our study provides preliminary evidence of a relationship between DNA methylation and inflammatory response to fenofibrate treatment.
机译：目的：用于治疗血脂血症的PPAR-α抑制剂，具有良好的抗炎作用，在个体之间变化。虽然DNA序列变化解释了一些观察到的响应变异性，但表观遗传模式呈现出由于PPAR-α通路，同型半胱氨酸和S-腺苷甲基硫甲硫醚 - 用于DNA甲基化反应的甲基源的生物连接而存在另一个有希望的调查途径。假设：基线的DNA甲基化变化与短期内纤维处理治疗的炎症反应有关。方法：我们对脂质降低药物和饮食网络遗传遗传学（Goldn，N = 750）的遗传学期间，在3周内进行了对每日治疗的第一种外形炎症反应的炎症反应研究。使用Illumina Infinuim甲基化450阵列在CD4（+）T细胞上定量外膜内甲基甲基化。结果：我们鉴定了多个CPG网站，显着与炎症细胞因子等血浆浓度的变化显着相关，例如高灵敏度CRP（HSCRP，7个CPG位点），IL-2可溶性受体（IL-2SR，一个CPG位点）和IL-6 （4个CPG网站）。映射到KIAA1324L（P = 2.63E-10），SMPD3（P = 2.14E-08），SYNPO2（P = 5.00E-08），ILF3（P = 1.04E07），PRR3，GNL1（P = 6.80） E-09），FAM50B（P = 3.19E-08），RPTOR（P = 9.79E-07）和几个基因区域（P <1.03E-07）。我们还使用主成分分析衍生出两种炎症模式，并在非伯纤维处理之前和之后未被覆盖的额外表观遗传次数。结论：我们的研究提供了DNA甲基化与对食纤维治疗的炎症反应关系的初步证据。

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