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 (r 2 = 0.219, p < 0.001, and r 2 = 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.

中文翻译：

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嗅觉通路基因甲基化标记、肥胖特征和饮食摄入之间的关联。

背景嗅觉是影响食物偏好、食欲和饮食行为的重要感觉。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之间的关联。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。研究人群的人体测量、临床数据和血清代谢谱来自 MENA 队列的结构化数据库。使用经过验证的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）在循环白细胞中测量 DNA 甲基化。FDR 值 (p < 0. 0001) 用于选择与体重指数 (BMI) 和腰围 (WC) 具有最佳相关性的 CpG。使用 KEGG 和 pathDIP 参考数据库进行涉及嗅觉转导系统所涉及基因表征的通路分析。结果 总体而言，在调整了潜在的混杂因素后，嗅觉通路基因的 15 个 CpG 位点与 BMI (p < 0.0001) 和 WC (p < 0.0001) 相关。总之，15 个 CpG 位点的甲基化水平占 BMI 和 WC 变异性的 22% 和 20%（分别为 r 2 = 0.219，p < 0.001 和 r 2 = 0.204，p < 0.001）。这些基因包括嗅觉受体（OR4D2、OR51A7、OR2T34 和 OR2Y1）和几个下游信号分子（SLC8A1、ANO2、PDE2A、CALML3、GNG7、CALML6、PRKG1 和 CAMK2D），正如通路富集分析所揭示的那样，它显着调节了整个嗅觉级联中的气味检测和信号转导过程 (p = 1.94 × 10-10)。此外，OR4D2 和 OR2Y1 基因甲基化模式与每日总能量 (p < 0.0001)、碳水化合物 (p < 0.0001)、蛋白质 (p < 0.0001) 和脂肪 (p < 0.0001) 的摄入量密切相关。结论 本研究结果表明嗅觉通路基因甲基化特征、肥胖指数和膳食摄入量之间存在新的关系。蛋白质 (p < 0.0001) 和脂肪 (p < 0.0001)。结论 本研究结果表明嗅觉通路基因甲基化特征、肥胖指数和膳食摄入量之间存在新的关系。蛋白质 (p < 0.0001) 和脂肪 (p < 0.0001)。结论 本研究结果表明嗅觉通路基因甲基化特征、肥胖指数和膳食摄入量之间存在新的关系。