Impact of Receptor Polymorphisms on Sensations from Common Oral Irritants

描述（由申请人提供）：感知差异可能代表了人类摄取行为遗传差异的一个重要方面（例如，为什么我们选择吃和喝一些食物和饮料，而不是其他的）。这一提议代表了化学感觉心理物理学、分子和定量行为遗传学研究人员之间的合作努力，以研究口腔中味觉和疼痛受体的遗传变异如何改变对食物中常见的口腔刺激物的反应。在这里，我们提出了一项实验室研究，以量化特定基因变异对辣椒素（辣椒的辣味成分）、胡椒碱（黑胡椒的辣味成分）和乙醇产生的感觉的影响。之前，我们发现辣椒素和胡椒碱对一些人来说是苦的，但对另一些人来说不是。现在，我们想知道苦味基因的遗传变异是否可以解释其中的原因。具体目标1-3项下的分析将确定TRPV1受体的常见多态性（基因的替代形式）是否预测了这些刺激物对烧灼感的不同反应。次要目的是测试苦味基因的某些变体是否可以解释这些刺激物的苦味差异。重要的协变量包括辛辣食物摄入的频率、个性因素（寻求新奇和寻求感觉）以及口腔感觉强度的潜在差异（超味觉）。在本项目结束时，我们将产生一系列有价值的数据，以解决遗传多态性对口腔刺激物烧伤和苦味的贡献。更好地了解刺激和苦味背后的生物学原理，将有助于开发阻止或掩盖这些感觉的方法，并有可能消除作为药物依从性障碍的适口性。拟议的工作也可能提供关于食物选择行为或涉及烧灼感的口腔病理原因的新见解。

DESCRIPTION (provided by applicant): Perceptual variation may represent an important aspect of genetic differences in human ingestive behavior (eg why we choose to eat and drink some foods and beverages but not others). This proposal represents a collaborative effort between investigators in chemosensory psychophysics, and molecular and quantitative behavioral genetics to examine how genetic variation in taste and pain receptors in the mouth may alter response to oral irritants that are commonly found in the food supply. Here, we propose a laboratory study to quantify the impact of variation in specific genes on the sensations that arise from capsaicin (the compound responsible for the heat of 'hot' peppers), piperine (the compound responsible for the burn of black pepper) and ethanol. Previously, we found capsaicin and piperine are bitter to some individuals but not others. Now, we ask if genetic variation in bitter taste genes can explain why. Analyses under Specific Aims 1-3 will determine if common polymorphisms (alternative forms of a gene) for the TRPV1 receptor predict differential response to the burning sensations from these irritants. Secondary aims test if certain variants of bitter taste genes can explain differences in the bitterness of these irritants. Important covariates include frequency of spicy food intake, personality factors (novelty seeking, and sensation seeking) and underlying differences in the intensity of oral sensations (supertasting). At the conclusion of this project, we will have produced a body of valuable data addressing the contribution of genetic polymorphisms on the burn and bitterness of oral irritants. Better understanding of the biology behind irritancy and bitterness will inform attempts to develop methods to block or mask these sensations and potentially remove palatability as a barrier to medication compliance. Proposed work may also provide new insight with respect to food choice behavior or causes of oral pathologies that involve burning sensations. PUBLIC HEALTH RELEVANCE: Taste is the main gatekeeper of ingestion: humans generally swallow what they like and reject what they don't, and what is liked may differ with genetics. This research examines whether the burning and bitterness from natural chemicals found in common spices are related to genetic differences in perception. Better understanding of the basic biology behind bitterness and irritancy will help us understand the dietary choices individuals make, and may help us tailor diets that improve health and wellness while remaining enjoyable to eat.