Genetic variation in the human olfactory receptor OR5AN1 associates with the perception of musks.
Genetic variation in the human olfactory receptor OR5AN1 associates with the perception of musks.
复制标题
人类嗅觉受体 OR5AN1 的遗传变异与麝香的感知有关。
DOI：
10.1093/chemse/bjac037
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发表时间：
2023
期刊：
影响因子：
3.5
通讯作者：
Touhara,Kazushige
中科院分区：
文献类型：
--
作者：
Sato-Akuhara,Narumi;Trimmer,Casey;Keller,Andreas;Niimura,Yoshihito;Shirasu,Mika;Mainland,JoelD;Touhara,Kazushige
人类在气味感知方面存在显著的个体差异，这源于他们的经验，有时也源于嗅觉受体（OR）基因库的差异。在某些情况下，单个OR的遗传变异会影响其同源气味配体的感知。麝香被广泛用于香料，并被称为表现出特定的嗅觉丧失。然而，还有待阐明的OR多态性是否有助于麝香气味感知的个体差异。先前的研究报道，人类麝香受体OR 5AN 1对各种麝香的体外反应与人类对这些气味的感知敏感性相关，并且小鼠直系同源物Olfr 1440（MOR 215 -1）在麝香酮感知中起着关键作用。在这里，我们利用OR 5AN 1的遗传变异来研究受体敏感性的变化如何与人类的麝香感知相关。我们在体外试验中研究了OR 5AN 1变体之间的功能差异，并测量了具有不同OR 5AN 1基因型的人类受试者的感知强度和检测阈值。人类受试者的更敏感的L289 F等位基因纯合子有一个较低的麝香酮的检测阈值，并发现大环麝香比受试者的参考等位基因纯合子更强烈。这些结果表明，OR 5AN 1的遗传变异有助于某些麝香的感知差异。此外，我们发现OR 5A 1的功能变体（一种参与β-紫罗兰酮感知的受体）与OR 5AN 1的功能变体相关，这表明大环麝香和β-紫罗兰酮的感知强度呈负相关。
Humans have significant individual variations in odor perception, derived from their experience or sometimes from differences in the olfactory receptor (OR) gene repertoire. In several cases, the genetic variation of a single OR affects the perception of its cognate odor ligand. Musks are widely used for fragrance and are known to demonstrate specific anosmia. It, however, remains to be elucidated whether the OR polymorphism contributes to individual variations in musk odor perception. Previous studies reported that responses of the human musk receptor OR5AN1 to a variety of musks in vitro correlated well with perceptual sensitivity to those odors in humans and that the mouse ortholog, Olfr1440 (MOR215-1), plays a critical role in muscone perception. Here, we took advantage of genetic variation in OR5AN1 to examine how changes in receptor sensitivity are associated with human musk perception. We investigated the functional differences between OR5AN1 variants in an in vitro assay and measured both perceived intensity and detection threshold in human subjects with different OR5AN1 genotypes. Human subjects homozygous for the more sensitive L289F allele had a lower detection threshold for muscone and found macrocyclic musks to be more intense than subjects homozygous for the reference allele. These results demonstrate that the genetic variation in OR5AN1 contributes to perceptual differences for some musks. In addition, we found that the more functional variant of OR5A1, a receptor involved in β-ionone perception, is associated with the less functional variant of OR5AN1, suggesting that the perceived intensities of macrocyclic musks and β-ionone are inversely correlated.