Irvin Marguerite R, Zhi Degui, Aslibekyan Stella, Claas Steven A, Absher Devin M, Ordovas Jose M, Tiwari Hemant K, Watkins Steve, Arnett Donna K
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
PLoS One. 2014 Jun 6;9(6):e99509. doi: 10.1371/journal.pone.0099509. eCollection 2014.
Increased postprandial lipid (PPL) response to dietary fat intake is a heritable risk factor for cardiovascular disease (CVD). Variability in postprandial lipids results from the complex interplay of dietary and genetic factors. We hypothesized that detailed lipid profiles (eg, sterols and fatty acids) may help elucidate specific genetic and dietary pathways contributing to the PPL response.
We used gas chromatography mass spectrometry to quantify the change in plasma concentration of 35 fatty acids and 11 sterols between fasting and 3.5 hours after the consumption of a high-fat meal (PPL challenge) among 40 participants from the GOLDN study. Correlations between sterols, fatty acids and clinical measures were calculated. Mixed linear regression was used to evaluate associations between lipidomic profiles and genomic markers including single nucleotide polymorphisms (SNPs) and methylation markers derived from the Affymetrix 6.0 array and the Illumina Methyl450 array, respectively. After the PPL challenge, fatty acids increased as well as sterols associated with cholesterol absorption, while sterols associated with cholesterol synthesis decreased. PPL saturated fatty acids strongly correlated with triglycerides, very low-density lipoprotein, and chylomicrons. Two SNPs (rs12247017 and rs12240292) in the sorbin and SH3 domain containing 1 (SORBS1) gene were associated with b-Sitosterol after correction for multiple testing (P≤4.5*10(-10)). SORBS1 has been linked to obesity and insulin signaling. No other markers reached the genome-wide significance threshold, yet several other biologically relevant loci are highlighted (eg, PRIC285, a co-activator of PPARa).
Integration of lipidomic and genomic data has the potential to identify new biomarkers of CVD risk.
餐后血脂（PPL）对膳食脂肪摄入的反应增强是心血管疾病（CVD）的一个可遗传风险因素。餐后血脂的变异性源于饮食和遗传因素的复杂相互作用。我们推测详细的血脂谱（如固醇和脂肪酸）可能有助于阐明导致PPL反应的特定遗传和饮食途径。
我们使用气相色谱-质谱法对来自GOLDN研究的40名参与者在食用高脂餐（PPL挑战）后禁食状态与3.5小时之间血浆中35种脂肪酸和11种固醇的浓度变化进行了定量分析。计算了固醇、脂肪酸与临床指标之间的相关性。分别使用混合线性回归来评估脂质组学谱与基因组标记之间的关联，这些基因组标记包括分别来自Affymetrix 6.0芯片和Illumina Methyl450芯片的单核苷酸多态性（SNP）和甲基化标记。在PPL挑战后，脂肪酸以及与胆固醇吸收相关的固醇增加，而与胆固醇合成相关的固醇减少。PPL饱和脂肪酸与甘油三酯、极低密度脂蛋白和乳糜微粒密切相关。经过多重检验校正后，含sorbin和SH3结构域蛋白1（SORBS1）基因中的两个SNP（rs12247017和rs12240292）与β-谷甾醇相关（P≤4.5×10⁻¹⁰）。SORBS1与肥胖和胰岛素信号传导有关。没有其他标记达到全基因组显著性阈值，但突出了其他几个具有生物学相关性的位点（如PRIC285，一种PPARα的共激活因子）。
脂质组学和基因组数据的整合有潜力识别心血管疾病风险的新生物标志物。
