Nature：OR7D4受体基因变异对气味感觉的影响

生物谷

不同人对特定气味的敏感性及他们对这些气味的主观体验都有很大差异。一项新的研究首次表明，人体一个单一气味受体中所发生的遗传变异与人的感觉差异相关。OR7D4是一种气味受体，在体外可被Androstenone选择性激发，后者是一种睾丸酮代谢物，被一些人认为是一种催情药，称作“佛洛蒙”。编码OR7D4的基因发生的变异会影响有这种变异的人是怎样想Androstenone的气味的——有些人认为它很好闻，另一些人则认为它很讨厌，还有一些人会发现它没有气味，同时也会影响人对这种气味的感觉。

英文原文：

Nature 449, 468-472 (27 September 2007) | doi:10.1038/nature06162; Received 20 June 2007; Accepted 8 August 2007; Published online 16 September 2007

Genetic variation in a human odorant receptor alters odour perception

Andreas Keller1,4, Hanyi Zhuang2,4, Qiuyi Chi2, Leslie B. Vosshall1 & Hiroaki Matsunami2,3

Laboratory of Neurogenetics and Behaviour, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA
Department of Molecular Genetics and Microbiology, and,
Department of Neurobiology, Duke University Medical Centre, Research Drive, Durham, North Carolina 27710, USA
These authors contributed equally to this work.

Correspondence to: Leslie B. Vosshall1Hiroaki Matsunami2,3 Correspondence and requests for materials should be addressed to H.M. (Email: hiroaki.matsunami@duke.edu) and L.B.V. (Email: leslie@mail.rockefeller.edu).

Human olfactory perception differs enormously between individuals, with large reported perceptual variations in the intensity and pleasantness of a given odour. For instance, androstenone (5 alpha -androst-16-en-3-one), an odorous steroid derived from testosterone, is variously perceived by different individuals as offensive ("sweaty, urinous"), pleasant ("sweet, floral") or odourless1, 2, 3. Similar variation in odour perception has been observed for several other odours4, 5, 6. The mechanistic basis of variation in odour perception between individuals is unknown. We investigated whether genetic variation in human odorant receptor genes accounts in part for variation in odour perception between individuals7, 8. Here we show that a human odorant receptor, OR7D4, is selectively activated in vitro by androstenone and the related odorous steroid androstadienone (androsta-4,16-dien-3-one) and does not respond to a panel of 64 other odours and two solvents. A common variant of this receptor (OR7D4 WM) contains two non-synonymous single nucleotide polymorphisms (SNPs), resulting in two amino acid substitutions (R88W, T133M; hence 'RT') that severely impair function in vitro. Human subjects with RT/WM or WM/WM genotypes as a group were less sensitive to androstenone and androstadienone and found both odours less unpleasant than the RT/RT group. Genotypic variation in OR7D4 accounts for a significant proportion of the valence (pleasantness or unpleasantness) and intensity variance in perception of these steroidal odours. Our results demonstrate the first link between the function of a human odorant receptor in vitro and odour perception.