Allele specific expression of TAS2R38 in human taste and nasal tissue

描述(申请人提供)：人类味觉系统可能提供一个了解人类健康的窗口。我们最近已经证明苦味受体T2R38在上呼吸道表达，并被酰基高丝氨酸内酯(AHLS)激活。AHLS是铜绿假单胞菌和其他革兰氏阴性细菌分泌的群体感应分子。此外，我们还发现，T2R38通过产生一氧化氮(NO)来调节人类上呼吸道的先天防御，从而刺激粘液纤毛清除，并具有直接的抗菌作用。此外，TAS2R38基因的常见多态赋予受体的功能，与对PTC分子的味道敏感性相关，与上呼吸道细胞对AHL反应清除和杀灭细菌的能力显著差异有关。该基因有三种常见的基因型，即纯合子显性、纯合子隐性和杂合子。在杂合子群体中发现了PTC味觉和AHL诱导的呼吸防御的最大程度的变异性。我们的假设是，TAS2R38多态的等位基因特异性表达预测了其在味觉和鼻腔组织中的功能。为了验证这一假设，我们将收集菌状味觉和鼻窦组织 25名接受鼻腔手术的杂合子患者有两个特定目的：(1)评估鼻腔上皮细胞的等位基因特异性表达，并确定这种表达是否持续存在，因为细胞在体外作为气液界面培养物生长，并与AHL诱导的呼吸防御相关；(2)评估真菌样乳头中的等位基因特异性表达，并确定其是否与PTC苦味感觉和鼻部的等位基因特异性表达相关。这些目的是为了更好地了解TAS2R38基因的功能性和非功能性变异在味觉和呼吸防御两个不同系统中的关系，并确定味觉是否可以用于临床预测呼吸道感染的严重程度。

DESCRIPTION (provided by applicant): The human taste system may provide a window on human health. We have recently demonstrated that the bitter taste receptor T2R38 is expressed in the upper airway and is activated by acyl-homoserine lactones (AHLs): quorum-sensing molecules secreted by Pseudomonas aeruginosa and other gram-negative bacteria. Furthermore, we found that T2R38 regulates human upper airway innate defenses through nitric oxide (NO) production, which stimulates mucociliary clearance and has direct antibacterial effects. Moreover, common polymorphisms of the TAS2R38 gene which confer functionality of the receptor, correlate with taste sensitivity to the molecule PTC are linked to significant differences in the ability of upper respiratory cells to clear and kill bacteria in response to AHL. There are three common genotypes for this gene, homozygous dominant, homozygous recessive and heterozygotes. The greatest degree of variability in both PTC taste perception and AHL induced respiratory defense are found in the heterozygote population. Our hypothesis is that allele specific expression of the TAS2R38 polymorphisms predict its function in taste and sinonasal tissue. To test this hypothesis we will collect fungiform taste and sinonasal tissue from 25 heterozygote patients undergoing sinonasal surgery for use in two specific aims: (1) to assess allele specific expression from the sinonasal epithelium and determine whether this persists as the cells are grown in vitro as air liquid interface cultures and correlates to AHL induced respiratory defenses and (2) assess allele specific expression in the fungiform papillae and determine whether it correlates with PTC bitter taste perception and the allele specific expression in the nose. The goal of these aims is to better understand the relationship of the functional and non-functional variants of the TAS2R38 gene in two distinct systems, taste and respiratory defense, and determine whether taste perception can be used clinically to predict severity of airway infection.