Omar Ramos-Lopez, Jose I Riezu-Boj, Fermin I Milagro, M Angeles Zulet, Jose L Santos, J Alfredo Martinez
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DNA methylation was measured in circulating white blood cells by microarray (Infinium Human Methylation 450 K BeadChips). FDR values (<i>p</i> < 0.0001) were used to select those CpGs that showed the best correlation with body mass index (BMI) and waist circumference (WC). Pathway analyses involving the characterization of genes involved in the olfactory transduction system were performed using KEGG and pathDIP reference databases.</p><p><strong>Results: </strong>Overall, 15 CpG sites at olfactory pathway genes were associated with BMI (<i>p</i> < 0.0001) and WC (<i>p</i> < 0.0001) after adjustments for potential confounding factors. Together, methylation levels at the15 CpG sites accounted for 22% and 20% of the variability in BMI and WC (<i>r</i> <sup>2</sup> = 0.219, <i>p</i> < 0.001, and <i>r</i> <sup>2</sup> = 0.204, <i>p</i> < 0.001, respectively). These genes encompassed olfactory receptors (<i>OR4D2</i>, <i>OR51A7</i>, <i>OR2T34</i>, and <i>OR2Y1</i>) and several downstream signaling molecules (<i>SLC8A1</i>, <i>ANO2</i>, <i>PDE2A</i>, <i>CALML3</i>, <i>GNG7</i>, <i>CALML6</i>, <i>PRKG1</i>, and <i>CAMK2D</i>), which significantly regulated odor detection and signal transduction processes within the complete olfactory cascade, as revealed by pathway enrichment analyses (<i>p</i> = 1.94 × 10<sup>-10</sup>). Moreover, <i>OR4D2</i> and <i>OR2Y1</i> gene methylation patterns strongly correlated with daily intakes of total energy (<i>p</i> < 0.0001), carbohydrates (<i>p</i> < 0.0001), protein (<i>p</i> < 0.0001), and fat (<i>p</i> < 0.0001).</p><p><strong>Conclusions: </strong>The results of this study suggest novel relationships between olfactory pathway gene methylation signatures, obesity indices, and dietary intakes.</p>","PeriodicalId":12554,"journal":{"name":"Genes & Nutrition","volume":"14 ","pages":"11"},"PeriodicalIF":0.0000,"publicationDate":"2019-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12263-019-0635-9","citationCount":"20","resultStr":"{\"title\":\"Associations between olfactory pathway gene methylation marks, obesity features and dietary intakes.\",\"authors\":\"Omar Ramos-Lopez, Jose I Riezu-Boj, Fermin I Milagro, M Angeles Zulet, Jose L Santos, J Alfredo Martinez\",\"doi\":\"10.1186/s12263-019-0635-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Olfaction is an important sense influencing food preferences, appetite, and eating behaviors. 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Pathway analyses involving the characterization of genes involved in the olfactory transduction system were performed using KEGG and pathDIP reference databases.</p><p><strong>Results: </strong>Overall, 15 CpG sites at olfactory pathway genes were associated with BMI (<i>p</i> < 0.0001) and WC (<i>p</i> < 0.0001) after adjustments for potential confounding factors. Together, methylation levels at the15 CpG sites accounted for 22% and 20% of the variability in BMI and WC (<i>r</i> <sup>2</sup> = 0.219, <i>p</i> < 0.001, and <i>r</i> <sup>2</sup> = 0.204, <i>p</i> < 0.001, respectively). These genes encompassed olfactory receptors (<i>OR4D2</i>, <i>OR51A7</i>, <i>OR2T34</i>, and <i>OR2Y1</i>) and several downstream signaling molecules (<i>SLC8A1</i>, <i>ANO2</i>, <i>PDE2A</i>, <i>CALML3</i>, <i>GNG7</i>, <i>CALML6</i>, <i>PRKG1</i>, and <i>CAMK2D</i>), which significantly regulated odor detection and signal transduction processes within the complete olfactory cascade, as revealed by pathway enrichment analyses (<i>p</i> = 1.94 × 10<sup>-10</sup>). 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引用次数: 20
摘要
背景:嗅觉是影响食物偏好、食欲和饮食行为的重要感官。这项假设驱动的研究旨在评估嗅觉通路基因甲基化特征、肥胖特征和饮食摄入量之间的关系。方法:对来自甲基表观基因组网络协会(MENA)项目的474名成年人进行营养表观基因组分析。从中东和北非队列的结构化数据库中获得了研究人群的人体测量值、临床数据和血清代谢谱。使用半定量食物频率问卷评估习惯性饮食摄入量。通过微阵列(Infinium Human methylation 450 K BeadChips)测量循环白细胞中的DNA甲基化。结果:总体而言，嗅觉通路基因上的15个CpG位点与BMI (p pr 2 = 0.219, pr 2 = 0.204, p pr 2 = OR4D2, OR51A7, OR2T34和OR2Y1)和几个下游信号分子(SLC8A1, ANO2, PDE2A, CALML3, GNG7, CALML6, PRKG1和CAMK2D)相关，这些信号分子在整个嗅觉级联中显著调节气味检测和信号转导过程，途径丰富分析显示(p = 1.94 × 10-10)。此外，OR4D2和OR2Y1基因甲基化模式与每日总能量摄入量密切相关(p p p p)。结论:本研究结果提示嗅觉通路基因甲基化特征、肥胖指数和饮食摄入量之间存在新的关系。
Associations between olfactory pathway gene methylation marks, obesity features and dietary intakes.
Background: Olfaction is an important sense influencing food preferences, appetite, and eating behaviors. This hypothesis-driven study aimed to assess associations between olfactory pathway gene methylation signatures, obesity features, and dietary intakes.
Methods: A nutriepigenomic analysis was conducted in 474 adults from the Methyl Epigenome Network Association (MENA) project. Anthropometric measurements, clinical data, and serum metabolic profiles of the study population were obtained from structured databases of the MENA cohorts. Habitual dietary intake was assessed using a validated semiquantitative food frequency questionnaire. DNA methylation was measured in circulating white blood cells by microarray (Infinium Human Methylation 450 K BeadChips). FDR values (p < 0.0001) were used to select those CpGs that showed the best correlation with body mass index (BMI) and waist circumference (WC). Pathway analyses involving the characterization of genes involved in the olfactory transduction system were performed using KEGG and pathDIP reference databases.
Results: Overall, 15 CpG sites at olfactory pathway genes were associated with BMI (p < 0.0001) and WC (p < 0.0001) after adjustments for potential confounding factors. Together, methylation levels at the15 CpG sites accounted for 22% and 20% of the variability in BMI and WC (r2 = 0.219, p < 0.001, and r2 = 0.204, p < 0.001, respectively). These genes encompassed olfactory receptors (OR4D2, OR51A7, OR2T34, and OR2Y1) and several downstream signaling molecules (SLC8A1, ANO2, PDE2A, CALML3, GNG7, CALML6, PRKG1, and CAMK2D), which significantly regulated odor detection and signal transduction processes within the complete olfactory cascade, as revealed by pathway enrichment analyses (p = 1.94 × 10-10). Moreover, OR4D2 and OR2Y1 gene methylation patterns strongly correlated with daily intakes of total energy (p < 0.0001), carbohydrates (p < 0.0001), protein (p < 0.0001), and fat (p < 0.0001).
Conclusions: The results of this study suggest novel relationships between olfactory pathway gene methylation signatures, obesity indices, and dietary intakes.
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