Genetic variation in the human olfactory receptor OR5AN1 associates with the perception of musks.

IF 2.8 4区 心理学 Q1 BEHAVIORAL SCIENCES
Narumi Sato-Akuhara, Casey Trimmer, Andreas Keller, Yoshihito Niimura, Mika Shirasu, Joel D Mainland, Kazushige Touhara
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引用次数: 0

Abstract

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.

人类嗅觉受体OR5AN1的遗传变异与麝香的感知有关。
人类在气味感知方面有显著的个体差异,这源于他们的经验,有时也源于嗅觉受体(or)基因库的差异。在一些情况下,单个OR的遗传变异会影响其同源气味配体的感知。麝香被广泛用于香水,并被认为是一种特殊的嗅觉。然而,OR多态性是否有助于麝香气味感知的个体差异仍有待阐明。先前的研究报道,人类麝香受体OR5AN1在体外对多种麝香的反应与人类对这些气味的感知敏感性密切相关,小鼠同源物Olfr1440 (MOR215-1)在麝香体感知中起着关键作用。在这里,我们利用OR5AN1的遗传变异来研究受体敏感性的变化如何与人类麝香感知相关。我们在体外实验中研究了OR5AN1变异之间的功能差异,并测量了不同OR5AN1基因型人类受试者的感知强度和检测阈值。L289F等位基因纯合的人对麝香体的检测阈值较低,发现大环麝香体比参考等位基因纯合的人更强烈。这些结果表明,OR5AN1的遗传变异有助于某些麝香的感知差异。此外,我们发现OR5A1(一种参与β-离子酮感知的受体)功能更强的变体与OR5AN1功能较弱的变体相关,这表明大环麝香和β-离子酮的感知强度呈负相关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Chemical Senses
Chemical Senses 医学-行为科学
CiteScore
8.60
自引率
2.90%
发文量
25
审稿时长
1 months
期刊介绍: Chemical Senses publishes original research and review papers on all aspects of chemoreception in both humans and animals. An important part of the journal''s coverage is devoted to techniques and the development and application of new methods for investigating chemoreception and chemosensory structures.
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